Arthur Cederbaum

Summary

Affiliation: Mount Sinai School of Medicine
Country: USA

Publications

  1. ncbi Nrf2 and Antioxidant Defense Against CYP2E1 Toxicity
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L Levy Place, 1603, New York, 10029, NY, USA
    Subcell Biochem 67:105-30. 2013
  2. ncbi CYP2E1 potentiates toxicity in obesity and after chronic ethanol treatment
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA
    Drug Metabol Drug Interact 27:125-44. 2012
  3. ncbi Alcohol metabolism
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Clin Liver Dis 16:667-85. 2012
  4. ncbi Role of CYP2E1 in ethanol-induced oxidant stress, fatty liver and hepatotoxicity
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, N Y, USA
    Dig Dis 28:802-11. 2010
  5. ncbi CYP2E1--biochemical and toxicological aspects and role in alcohol-induced liver injury
    Arthur I Cederbaum
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, New York, NY 10029, USA
    Mt Sinai J Med 73:657-72. 2006
  6. ncbi Role of oxidative stress in alcohol-induced liver injury
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Arch Toxicol 83:519-48. 2009
  7. ncbi Iron and CYP2E1-dependent oxidative stress and toxicity
    Arthur I Cederbaum
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, New York, NY 10029, USA
    Alcohol 30:115-20. 2003
  8. ncbi Cytochrome P450 2E1-dependent oxidant stress and upregulation of anti-oxidant defense in liver cells
    Arthur I Cederbaum
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York 10029, USA
    J Gastroenterol Hepatol 21:S22-5. 2006
  9. ncbi CYP2E1-dependent toxicity and oxidative stress in HepG2 cells
    A I Cederbaum
    Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 31:1539-43. 2001
  10. ncbi Nrf2 and antioxidant defense against CYP2E1 toxicity
    Arthur Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Expert Opin Drug Metab Toxicol 5:1223-44. 2009

Research Grants

  1. Degradation of Human CYP2E1 by the Proteasome
    Arthur Cederbaum; Fiscal Year: 2004
  2. Modulation by SAMe of CYP2E1-dependent Effects in Liver.
    Arthur Cederbaum; Fiscal Year: 2006
  3. ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1
    Arthur Cederbaum; Fiscal Year: 2006
  4. Effects of ethanol and CYP2E1 on liver function
    Arthur Cederbaum; Fiscal Year: 2007
  5. Alcohol-Induced Fatty Liver and Injury in Humanized CYP2E1 Knockin Mice.
    Arthur Cederbaum; Fiscal Year: 2009
  6. Role of CYP2E1 in TNFa-Ethanol -induced Liver Injury
    Arthur I Cederbaum; Fiscal Year: 2010
  7. ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1
    Arthur Cederbaum; Fiscal Year: 2002
  8. EFFECTS OF ETHANOL AND ACETALDEHYDE ON LIVER FUNCTION
    Arthur Cederbaum; Fiscal Year: 1993
  9. ETHANOL AND ACETALDEHYDE EFFECTS ON LIVER FUNCTION
    Arthur Cederbaum; Fiscal Year: 1999
  10. ALCOHOL OXYGEN RADICAL INTERACTIONS AS DETECTED BY ESR
    Arthur Cederbaum; Fiscal Year: 2001

Detail Information

Publications84

  1. ncbi Nrf2 and Antioxidant Defense Against CYP2E1 Toxicity
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L Levy Place, 1603, New York, 10029, NY, USA
    Subcell Biochem 67:105-30. 2013
    ..These results suggest that Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1 in the HepG2 cells...
  2. ncbi CYP2E1 potentiates toxicity in obesity and after chronic ethanol treatment
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA
    Drug Metabol Drug Interact 27:125-44. 2012
    ..Collectively, these studies show that CYP2E1 contributes to ethanol-induced and obesity-induced oxidant stress and liver injury...
  3. ncbi Alcohol metabolism
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Clin Liver Dis 16:667-85. 2012
    ..The kinetics of alcohol elimination in-vivo and the various genetic and environmental factors that can modify the rate of alcohol metabolism are discussed...
  4. ncbi Role of CYP2E1 in ethanol-induced oxidant stress, fatty liver and hepatotoxicity
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, N Y, USA
    Dig Dis 28:802-11. 2010
    ..There is a need to develop oral models of significant ethanol-induced liver injury and to evaluate the possible role of CYP2E1 in ethanol actions in such models...
  5. ncbi CYP2E1--biochemical and toxicological aspects and role in alcohol-induced liver injury
    Arthur I Cederbaum
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, New York, NY 10029, USA
    Mt Sinai J Med 73:657-72. 2006
    ..Regulation of CYP2E1 is quite complex and will be briefly reviewed. Future directions in research, which may help clarify the actions of CYP2E1 and its role in alcoholic liver injury, are suggested...
  6. ncbi Role of oxidative stress in alcohol-induced liver injury
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Arch Toxicol 83:519-48. 2009
    ..Special emphasis is placed on CYP2E1, which is induced by alcohol and is reactive in metabolizing and activating many hepatotoxins, including ethanol, to reactive products, and in generating ROS...
  7. ncbi Iron and CYP2E1-dependent oxidative stress and toxicity
    Arthur I Cederbaum
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, New York, NY 10029, USA
    Alcohol 30:115-20. 2003
    ..Such interactions may play a role in alcohol-induced liver injury...
  8. ncbi Cytochrome P450 2E1-dependent oxidant stress and upregulation of anti-oxidant defense in liver cells
    Arthur I Cederbaum
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York 10029, USA
    J Gastroenterol Hepatol 21:S22-5. 2006
    ..These results suggest that Nrf2 is activated and its levels are increased when CYP2E1 is elevated. It is suggested that Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1...
  9. ncbi CYP2E1-dependent toxicity and oxidative stress in HepG2 cells
    A I Cederbaum
    Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 31:1539-43. 2001
    ..HepG2 cell lines overexpressing CYP2E1 may be a valuable model to characterize the biochemical and toxicological properties of CYP2E1...
  10. ncbi Nrf2 and antioxidant defense against CYP2E1 toxicity
    Arthur Cederbaum
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Expert Opin Drug Metab Toxicol 5:1223-44. 2009
    ....
  11. ncbi Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver injury
    Arthur I Cederbaum
    Department of Pharmacology and Systems Therapeutics, Box 1603, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
    World J Gastroenterol 16:1366-76. 2010
    ..This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection...
  12. ncbi Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Box 1603, One Gustave L. Levy Place, Mount Sinai School of Medicine, New York, NY 10029, USA
    Toxicol Appl Pharmacol 216:282-92. 2006
    ..These results indicate that NO can be hepatoprotective against CYP2E1-dependent toxicity, preventing AA-induced oxidative stress...
  13. ncbi Development and properties of HepG2 cells that constitutively express CYP2E1
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY, USA
    Methods Mol Biol 447:137-50. 2008
    ..Methods are described as to how the cell lines were established and maintained, how CYP2E1 is assayed, how cellular viability, mitochondrial function and generation of oxidant stress are determined...
  14. ncbi Overexpression of CYP2E1 in mitochondria sensitizes HepG2 cells to the toxicity caused by depletion of glutathione
    Jingxiang Bai
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 281:5128-36. 2006
    ..The accumulation of CYP2E1 in hepatic mitochondria induced by ethanol consumption might play an important role in alcohol liver disease...
  15. ncbi Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1
    Pengfei Gong
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hepatology 43:144-53. 2006
    ..These results suggest that Nrf2 is activated and that levels of protein and mRNA are increased when CYP2E1 is elevated. In conclusion, Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1...
  16. ncbi Role of phospholipase A2 activation and calcium in CYP2E1-dependent toxicity in HepG2 cells
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:33866-77. 2003
    ....
  17. ncbi Cytochrome P450 2E1 responsiveness in the promoter of glutamate-cysteine ligase catalytic subunit
    Natalia Nieto
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Hepatology 37:96-106. 2003
    ....
  18. ncbi Increased expression of cytochrome P450 2E1 induces heme oxygenase-1 through ERK MAPK pathway
    Pengfei Gong
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:29693-700. 2003
    ..This induction may serve as an adaptive mechanism to protect the E47 cells against the CYP2E1-dependent oxidative stress...
  19. ncbi Pyrazole induced oxidative liver injury independent of CYP2E1/2A5 induction due to Nrf2 deficiency
    Yongke Lu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Toxicology 252:9-16. 2008
    ..In summary, even though ROS-producing CYP2E1/2A5 were not elevated by pyrazole, impaired antioxidant capacity resulting from Nrf2 deficiency appear to be sufficient to promote pyrazole-induced oxidative liver injury...
  20. ncbi Cytochrome P4502E1 sensitizes to tumor necrosis factor alpha-induced liver injury through activation of mitogen-activated protein kinases in mice
    Defeng Wu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA
    Hepatology 47:1005-17. 2008
    ..CONCLUSION: These results show that CYP2E1 sensitizes liver hepatocytes to LPS or TNF-alpha and that the CYP2E1-enhanced LPS or TNF-alpha injury, oxidant stress, and mitochondrial injury is JNK or p38 MAPK dependent...
  21. ncbi Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against toxicity caused by glutathione depletion in HepG2 cells expressing CYP2E1
    Montserrat Mari
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Pharmacol Exp Ther 301:111-8. 2002
    ..Damage to mitochondria may be a critical step for cellular toxicity by CYP2E1-derived reactive oxygen species...
  22. ncbi Transcription factor Nrf2 protects HepG2 cells against CYP2E1 plus arachidonic acid-dependent toxicity
    Pengfei Gong
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    J Biol Chem 281:14573-9. 2006
    ..Together, these results suggest that Nrf2, through up-regulation of glutamate-cysteine ligase and increase of GSH levels, protects against CYP2E1-dependent AA toxicity...
  23. ncbi The mode of cisplatin-induced cell death in CYP2E1-overexpressing HepG2 cells: modulation by ERK, ROS, glutathione, and thioredoxin
    Yongke Lu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 43:1061-75. 2007
    ....
  24. ncbi Activation of ASK-1 and downstream MAP kinases in cytochrome P4502E1 potentiated tumor necrosis factor alpha liver injury
    Defeng Wu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 49:348-60. 2010
    ..We speculate that similar interactions between CYP2E1 and TNFalpha may be important for alcohol-induced liver injury...
  25. ncbi Metallothionein 2A induction by zinc protects HEPG2 cells against CYP2E1-dependent toxicity
    Maria José Perez
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 34:443-55. 2003
    ..MT may have potential clinical utility for the prevention or improvement of liver injury produced by agents known to be metabolized by CYP2E1 to reactive intermediates and to cause oxidative stress...
  26. ncbi Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells
    Natalia Nieto
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 277:9853-64. 2002
    ..These co-culture models may be useful for understanding the impact of CYP2E1-derived ROS on stellate cell function and activation...
  27. ncbi Enhancement by pyrazole of lipopolysaccharide-induced liver injury in mice: role of cytochrome P450 2E1 and 2A5
    Yongke Lu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hepatology 44:263-74. 2006
    ..In conclusion, induction of CYP2E1 plays an important role in the enhancement of LPS liver injury by pyrazole, but some contribution by CYP2A5 cannot be excluded...
  28. ncbi Serum deprivation-induced HepG2 cell death is potentiated by CYP2E1
    Jian Zhuge
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Place, New York, NY 10029, USA
    Free Radic Biol Med 40:63-74. 2006
    ..Potentiation of serum deprivation-induced cell death by CYP2E1 may contribute to the sensitivity of the liver to alcohol-induced ischemia and growth factor deprivation...
  29. ncbi Cyclosporine A protects against arachidonic acid toxicity in rat hepatocytes: role of CYP2E1 and mitochondria
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    Hepatology 35:1420-30. 2002
    ..In conclusion, damage to mitochondria appears to play an important role in the CYP2E1 plus AA toxicity...
  30. ncbi Antioxidant and pro-oxidant effects of a manganese porphyrin complex against CYP2E1-dependent toxicity
    Maria José Perez
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 33:111-27. 2002
    ....
  31. ncbi Green tea polyphenol epigallocatechin-3-gallate protects HepG2 cells against CYP2E1-dependent toxicity
    Jose M Jimenez-Lopez
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 36:359-70. 2004
    ....
  32. ncbi Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species
    Natalia Nieto
    Department of Biochemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
    Hepatology 35:62-73. 2002
    ..Thus, besides perturbing the homeostasis of hepatocytes, CYP2E1-derived diffusible oxidants may also interact with stellate cells and contribute to hepatic fibrosis...
  33. ncbi Role of nitric oxide and nuclear factor-kappaB in the CYP2E1 potentiation of tumor necrosis factor alpha hepatotoxicity in mice
    Defeng Wu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 46:480-91. 2009
    ..These effects combine with the blunting of the NF-kappaB activation pathways and the synthesis of protective factors to cause liver injury...
  34. ncbi Alcohol and oxidative liver injury
    Aparajita Dey
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY, USA
    Hepatology 43:S63-74. 2006
    ..Many of the seminal reports in this topic have been published in Hepatology , and it is fitting to review this research area for the 25th Anniversary Issue of the Journal...
  35. ncbi Depletion of S-adenosyl-l-methionine with cycloleucine potentiates cytochrome P450 2E1 toxicity in primary rat hepatocytes
    Jian Zhuge
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Arch Biochem Biophys 466:177-85. 2007
    ..This is due to elevated ROS production by CYP2E1 coupled to lower levels of hepatoprotective SAM and GSH. We speculate that such interactions e.g. induction of CYP2E1, decline in SAM and GSH may contribute to alcohol liver toxicity...
  36. ncbi Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice
    Aparajita Dey
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Hepatology 45:1355-65. 2007
    ..CONCLUSION: These results show that obesity contributes to oxidative stress and liver injury and that induction of CYP2E1 enhances these effects...
  37. ncbi Increased toxicity by transforming growth factor-beta 1 in liver cells overexpressing CYP2E1
    Jian Zhuge
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Place, New York, NY 10029, USA
    Free Radic Biol Med 41:1100-12. 2006
    ..Potentiation of TGF-beta1-induced cell death by CYP2E1 may contribute to mechanisms of alcohol-induced liver disease...
  38. ncbi Adenovirus-mediated expression of Cu/Zn- or Mn-superoxide dismutase protects against CYP2E1-dependent toxicity
    Maria José Perez
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hepatology 38:1146-58. 2003
    ..In conclusion, these enzymes may be useful in the prevention or improvement of liver injury produced by agents known to be metabolized by CYP2E1 to reactive intermediates and to cause oxidative stress...
  39. ncbi Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1
    Yongke Lu
    The Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Toxicol Sci 89:515-23. 2006
    ..Both in vitro and in vivo results indicate that elevated CYP2E1 enhances cisplatin-induced hepatotoxicity, and the mechanism may involve increased production of ROS and oxidative stress...
  40. ncbi Ca2+-dependent and independent mitochondrial damage in HepG2 cells that overexpress CYP2E1
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Arch Biochem Biophys 408:162-70. 2002
    ..Ca(2+) mobilization and activation of calpain contributes to the more rapid onset of mitochondrial damage in MEM, while oxidative damage and lipid peroxidation are involved in the Ca(2+)-independent later onset of mitochondrial damage...
  41. ncbi Proteasome inhibition potentiates CYP2E1-mediated toxicity in HepG2 cells
    Maria José Perez
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hepatology 37:1395-404. 2003
    ..Such interactions may be important in CYP2E1-catalyzed toxicity of hepatotoxins and in alcohol-induced liver injury...
  42. ncbi Oxidative stress and alcoholic liver disease
    Defeng Wu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Semin Liver Dis 29:141-54. 2009
    ..Many pathways play a key role in how ethanol induces oxidative stress. This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced liver injury...
  43. ncbi CYP2E1 enhances ethanol-induced lipid accumulation but impairs autophagy in HepG2 E47 cells
    Defeng Wu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Biochem Biophys Res Commun 402:116-22. 2010
    ..We hypothesize that CYP2E1-induced oxidative stress promotes the accumulation of lipid droplets by ethanol and this may be responsible for the suppression of autophagy in the liver...
  44. ncbi The liver-selective nitric oxide donor O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) protects HepG2 cells against cytochrome P450 2E1-dependent toxicity
    Pengfei Gong
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029
    Mol Pharmacol 65:130-8. 2004
    ....
  45. ncbi Chronic ethanol feeding potentiates Fas Jo2-induced hepatotoxicity: role of CYP2E1 and TNF-alpha and activation of JNK and P38 MAP kinase
    Xiaodong Wang
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 47:518-28. 2009
    ..These results show that chronic ethanol feeding enhances Fas-induced liver injury by a mechanism associated with induction of CYP2E1, elevated serum TNF-alpha levels, and activation of MAPK...
  46. ncbi Role of calcium and calcium-activated proteases in CYP2E1-dependent toxicity in HEPG2 cells
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 277:104-13. 2002
    ..These results suggest that CYP2E1-dependent toxicity in this model depends on the activation of lipid peroxidation, followed by an increased influx of extracellular Ca2+ and activation of Ca2+-dependent proteases...
  47. ncbi Lipopolysaccharide-induced liver injury in rats treated with the CYP2E1 inducer pyrazole
    Yongke Lu
    Dept. of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, One Gustave L. Levy Place, New York, NY 10029, USA
    Am J Physiol Gastrointest Liver Physiol 289:G308-19. 2005
    ..The enhanced liver necrosis appears to involve an increase in oxidative and nitrosative stress generated by the combination of LPS plus elevated CYP2E1 levels...
  48. ncbi S-adenosyl-L-methionine attenuates hepatotoxicity induced by agonistic Jo2 Fas antibody following CYP2E1 induction in mice
    Xiaodong Wang
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Pharmacol Exp Ther 317:44-52. 2006
    ..These results indicate that SAM can have an important hepatoprotective role as an effective reagent against Fas plus CYP2E1-induced hepatotoxicity by lowering oxidative and nitrosative stress...
  49. ncbi S-adenosyl-L-methionine decreases the elevated hepatotoxicity induced by Fas agonistic antibody plus acute ethanol pretreatment in mice
    Xiaodong Wang
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L Levy Place, 1468 Madison Avenue, New York, NY 10029, USA
    Arch Biochem Biophys 477:1-11. 2008
    ....
  50. ncbi Glutathione depletion in CYP2E1-expressing liver cells induces toxicity due to the activation of p38 mitogen-activated protein kinase and reduction of nuclear factor-kappaB DNA binding activity
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
    Mol Pharmacol 66:749-60. 2004
    ..This loss, coupled to CYP2E1-generated oxidant stress, synergize to promote cell injury...
  51. ncbi Synergistic toxicity induced by prolonged glutathione depletion and inhibition of nuclear factor-kappaB signaling in liver cells
    Jose M Jimenez-Lopez
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Toxicol In Vitro 22:106-15. 2008
    ..In summary, inhibition of NF-kappaB sensitizes liver cells to toxicity linked to GSH depletion, probably accelerating the processes of thiol homeostasis deregulation and induction of apoptosis through a mechanism mediated by p38 MAPK...
  52. ncbi Inhibition of the mitochondrial permeability transition by cyclosporin A prevents pyrazole plus lipopolysaccharide-induced liver injury in mice
    Jian Zhuge
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 46:406-13. 2009
    ..These results indicate that mitochondria are the critical targets of pyrazole plus LPS in mediating liver injury...
  53. ncbi Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice
    Xiaodong Wang
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
    Hepatology 42:400-10. 2005
    ..In conclusion, enhanced hepatotoxicity of Fas was found in mice with elevated levels of CYP2E1. We speculate that overexpression of CYP2E1 might synergize and increase the susceptibility to Fas induced-liver injury...
  54. ncbi Adenovirus mediated overexpression of CYP2E1 increases sensitivity of HepG2 cells to acetaminophen induced cytotoxicity
    Jingxiang Bai
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York 10029, USA
    Mol Cell Biochem 262:165-76. 2004
    ..The Ad-CYP2E1 may be useful for studies designed to investigate the role of CYP2E1 in APAP and alcoholic liver injury and to further characterize the actions and effects of CYP2E1...
  55. ncbi Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production
    Meihui Pan
    The Zena and Michael A Wiener Cardiovascular Institute and the Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
    J Clin Invest 113:1277-87. 2004
    ....
  56. ncbi Heme oxygenase-1 protects HepG2 cells against cytochrome P450 2E1-dependent toxicity
    Pengfei Gong
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 36:307-18. 2004
    ..These results suggest that induction of HO-1 protects against CYP2E1-dependent toxicity and this protection may be mediated in part via production of CO and CO inhibition of CYP2E1 activity...
  57. ncbi Opposite action of S-adenosyl methionine and its metabolites on CYP2E1-mediated toxicity in pyrazole-induced rat hepatocytes and HepG2 E47 cells
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Am J Physiol Gastrointest Liver Physiol 290:G674-84. 2006
    ..In conclusion, contrasting effects of SAMe on CYP2E1 toxicity were observed in pyrazole hepatocytes and E47 cells. In hepatocytes, SAMe protects against CYP2E1 toxicity by a mechanism involving maintaining or elevating GSH levels...
  58. ncbi S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury
    Aparajita Dey
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Am J Physiol Gastrointest Liver Physiol 293:G91-103. 2007
    ..In conclusion, SAM protects against and can also reverse or correct CYP2E1-induced liver damage in ob/ob mice...
  59. ncbi Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice
    Yongke Lu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hepatology 47:1483-94. 2008
    ....
  60. ncbi Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Toxicol Appl Pharmacol 207:70-6. 2005
    ..HepG2 cell lines overexpressing CYP2E1 may be a valuable model to characterize the biochemical and toxicological properties of CYP2E1...
  61. ncbi The effect of CYP2E1-dependent oxidant stress on activity of proteasomes in HepG2 cells
    Irina G Kessova
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Pharmacol Exp Ther 315:304-12. 2005
    ....
  62. ncbi CYP2E1: biochemistry, toxicology, regulation and function in ethanol-induced liver injury
    Irina Kessova
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Curr Mol Med 3:509-18. 2003
    ....
  63. ncbi Protein kinase C signaling as a survival pathway against CYP2E1-derived oxidative stress and toxicity in HepG2 cells
    Jose M Jimenez-Lopez
    Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
    J Pharmacol Exp Ther 312:998-1006. 2005
    ..In conclusion, PKC activation by TPA prevents CYP2E1-derived acute oxidative stress and toxicity in HepG2 cells, and this appears to involve maintenance of the intracellular redox homeostasis via PKC signal transduction...
  64. ncbi Alcohol-induced liver injury in mice lacking Cu, Zn-superoxide dismutase
    Irina G Kessova
    Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hepatology 38:1136-45. 2003
    ..We speculate that the increased oxidative stress causes mitochondrial damage and reduction of ATP content, leading to alcoholic liver injury. This model may be useful in further mechanistic studies on alcohol-induced liver injury...
  65. ncbi Antioxidant properties of S-adenosyl-L-methionine in Fe(2+)-initiated oxidations
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 36:1303-16. 2004
    ..This could represent an important mechanism by which SAM exerts cellular protective actions and reduces oxidative stress in biological systems...
  66. ncbi Binge ethanol exposure increases liver injury in obese rats
    Michal Carmiel-Haggai
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, and Division of Livers Diseases, Mount Sinai Medical Center, New York, New York 10029, USA
    Gastroenterology 125:1818-33. 2003
    ..The objective of this study was to address the hepatic effects of acute alcohol consumption in obesity by simulating an alcohol binge in genetically obese fa/fa rats compared with lean Fa/? rats...
  67. ncbi Geldanamycin, an inhibitor of Hsp90, potentiates cytochrome P4502E1-mediated toxicity in HepG2 cells
    Aparajita Dey
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    J Pharmacol Exp Ther 317:1391-9. 2006
    ..These results suggest that Hsp90 is protective against CYP2E1-dependent oxidant stress and loss of cell viability in HepG2 cells...
  68. ncbi S-adenosylmethionine blocks collagen I production by preventing transforming growth factor-beta induction of the COL1A2 promoter
    Natalia Nieto
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 280:30963-74. 2005
    ..These observations unveil a novel mechanism by which AdoMet could ameliorate liver fibrosis...
  69. ncbi Cycloheximide protects HepG2 cells from serum withdrawal-induced apoptosis by decreasing p53 and phosphorylated p53 levels
    Jingxiang Bai
    Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    J Pharmacol Exp Ther 319:1435-43. 2006
    ..In summary, CHX protects HepG2 cells from serum withdrawal-induced apoptosis through inhibiting the synthesis of p53 and the phosphorylation of p53...
  70. ncbi Adenovirus-mediated expression of CYP2E1 produces liver toxicity in mice
    Jingxiang Bai
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Toxicol Sci 91:365-71. 2006
    ..These results show that adenovirus-mediated overexpression of CYP2E1 could induce liver toxicity in mice and suggests a mechanism involving oxidative/nitrosative stress...
  71. ncbi Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Biochem Pharmacol 69:1081-93. 2005
    ....
  72. ncbi Toxicity by pyruvate in HepG2 cells depleted of glutathione: role of mitochondria
    Montserrat Mari
    Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
    Free Radic Biol Med 32:73-83. 2002
    ....
  73. ncbi CYP2E1 and oxidative liver injury by alcohol
    Yongke Lu
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Free Radic Biol Med 44:723-38. 2008
    ....
  74. ncbi CYP2E1-dependent oxidative stress and toxicity: role in ethanol-induced liver injury
    Jose M Jimenez-Lopez
    Mount Sinai School of Medicine, Department of Pharmacology and Biological Chemistry, New York, NY 10029, USA
    Expert Opin Drug Metab Toxicol 1:671-85. 2005
    ..Future directions, which may help to better understand the actions of CYP2E1 and its role in alcoholic liver injury, are suggested...
  75. ncbi Oxidative stress, toxicology, and pharmacology of CYP2E1
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Annu Rev Pharmacol Toxicol 44:27-42. 2004
    ..We believe that the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, and GSH homeostasis contribute to the toxic actions of ethanol on the liver...
  76. ncbi Ethanol induction of CYP2A5: permissive role for CYP2E1
    Yongke Lu
    Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Drug Metab Dispos 39:330-6. 2011
    ..The possibility that induction of CYP2E1 is permissive for the induction of CYP2A5 may reflect a new contribution by CYP2E1 to the actions of ethanol...
  77. ncbi Role of p38 MAPK in CYP2E1-dependent arachidonic acid toxicity
    Defeng Wu
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York University, New York 10029, USA
    J Biol Chem 278:1115-24. 2003
    ..Activation of p38 MAPK by AA coupled to AA-induced oxidative stress may synergize to cause cell toxicity by affecting mitochondrial membrane potential and by modulation of NF-kappaB activation...
  78. ncbi Role of intracellular calcium and phospholipase A2 in arachidonic acid-induced toxicity in liver cells overexpressing CYP2E1
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Arch Biochem Biophys 457:252-63. 2007
    ..These interactions may play a role in alcohol liver toxicity, which requires polyunsaturated fatty acids, and involves induction of CYP2E1...
  79. ncbi Increased Sp1-dependent transactivation of the LAMgamma 1 promoter in hepatic stellate cells co-cultured with HepG2 cells overexpressing cytochrome P450 2E1
    Natalia Nieto
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:15360-72. 2003
    ..These results show that diffusable CYP2E1-derived oxidative-stress mediators induce synthesis of laminins by a transcriptional mechanism in HSC. Such interactions between hepatocytes and HSC may be important during liver fibrosis...
  80. ncbi Mitochondrial alterations in livers of Sod1-/- mice fed alcohol
    Irina G Kessova
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Free Radic Biol Med 42:1470-80. 2007
    ....
  81. ncbi Role of phosphatidylinositol 3-kinase/AKT as a survival pathway against CYP2E1-dependent toxicity
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    J Pharmacol Exp Ther 318:360-72. 2006
    ....
  82. ncbi Metabolism of a liver-selective nitric oxide-releasing agent, V-PYRRO/NO, by human microsomal cytochromes P450
    Keiko Inami
    Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702, USA
    Nitric Oxide 14:309-15. 2006
    ..The results confirm the proposed activation mechanism involving enzymatic oxidation of the vinyl group in V-PYRRO/NO followed by epoxide hydration and hydrolytic decomposition of the resulting PYRRO/NO ion to generate nitric oxide...
  83. ncbi Use of CYP2E1-transfected human liver cell lines in elucidating the actions of ethanol
    Raj Lakshman
    Lipid Research Laboratory, VA Medical Center, and the Department of Biochemistry, Molecular Biology, and Medicine, George Washington University, Washington, DC 20422, USA
    Alcohol Clin Exp Res 29:1726-34. 2005
    ..Donohue...
  84. ncbi Role of cytochrome P450 in phospholipase A2- and arachidonic acid-mediated cytotoxicity
    Andres A Caro
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    Free Radic Biol Med 40:364-75. 2006
    ..Inhibition of specific PLA2 and cytochrome P450 isoforms may represent novel therapeutic strategies against these diseases...

Research Grants39

  1. Degradation of Human CYP2E1 by the Proteasome
    Arthur Cederbaum; Fiscal Year: 2004
    ..Modulators of any of these newly identified steps may have therapeutic implications for individuals with high levels of CYP2E1. ..
  2. Modulation by SAMe of CYP2E1-dependent Effects in Liver.
    Arthur Cederbaum; Fiscal Year: 2006
    ....
  3. ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1
    Arthur Cederbaum; Fiscal Year: 2006
    ..It is hoped that such studies in hepatocyte and HepG2 cell culture models and in-vivo models, will help to define further the biochemical and toxicological actions of CYP2E1 and its role in alcohol-induced liver injury. ..
  4. Effects of ethanol and CYP2E1 on liver function
    Arthur Cederbaum; Fiscal Year: 2007
    ....
  5. Alcohol-Induced Fatty Liver and Injury in Humanized CYP2E1 Knockin Mice.
    Arthur Cederbaum; Fiscal Year: 2009
    ..Identification of downstream effectors of alcohol/CYP2E1 actions would be very informative in developing therapeutic interventions against alcohol-induced liver injury and fatty liver. ..
  6. Role of CYP2E1 in TNFa-Ethanol -induced Liver Injury
    Arthur I Cederbaum; Fiscal Year: 2010
    ..The latter may have potential therapeutic value. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page ..
  7. ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1
    Arthur Cederbaum; Fiscal Year: 2002
    ..It is hoped that these studies will help to define the role of CYP2E1 and CYP2E1-derived reactive oxygen species in the hepatotoxic actions of ethanol. ..
  8. EFFECTS OF ETHANOL AND ACETALDEHYDE ON LIVER FUNCTION
    Arthur Cederbaum; Fiscal Year: 1993
    ....
  9. ETHANOL AND ACETALDEHYDE EFFECTS ON LIVER FUNCTION
    Arthur Cederbaum; Fiscal Year: 1999
    ....
  10. ALCOHOL OXYGEN RADICAL INTERACTIONS AS DETECTED BY ESR
    Arthur Cederbaum; Fiscal Year: 2001
    ..These studies will provide new information on the ability of NO to modulate CYP2El catalytic activity, generation of reactive intermediates, and ethanol and PUFA toxicity. ..
  11. Alcohol-Induced Fatty Liver and Injury in Humanized CYP2E1 Knockin Mice.
    Arthur I Cederbaum; Fiscal Year: 2010
    ..Identification of downstream effectors of alcohol/CYP2E1 actions would be very informative in developing therapeutic interventions against alcohol-induced liver injury and fatty liver. ..