Pdk4

Summary

Gene Symbol: Pdk4
Description: pyruvate dehydrogenase kinase, isozyme 4
Alias: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial, pyruvate dehydrogenase kinase, isoenzyme 4, pyruvate dehydrogenate kinase 4
Species: rat

Top Publications

  1. pmc Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex
    M M Bowker-Kinley
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202 5122, USA
    Biochem J 329:191-6. 1998
  2. pmc FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate
    Lin Piao
    Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL, USA
    J Mol Med (Berl) 91:333-46. 2013
  3. ncbi Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase
    L G Korotchkina
    Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214, USA
    J Biol Chem 276:37223-9. 2001
  4. ncbi Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases
    M S Patel
    Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214, USA
    Exp Mol Med 33:191-7. 2001
  5. ncbi Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy
    Guixiang Zhao
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9041, USA
    Am J Physiol Heart Circ Physiol 294:H936-43. 2008
  6. pmc Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue
    Thomas Cadoudal
    Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche S 747, Universite Paris Descartes, Centre Universitaire des Saints Peres, Paris, France
    Diabetes 57:2272-9. 2008
  7. doi Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids
    S M Houten
    Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
    Cell Mol Life Sci 66:1283-94. 2009
  8. pmc Regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) gene expression by glucocorticoids and insulin
    Sara Connaughton
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA
    Mol Cell Endocrinol 315:159-67. 2010
  9. pmc Regulation of pyruvate dehydrogenase kinase 4 (PDK4) by thyroid hormone: role of the peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha)
    Ramy R Attia
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Biol Chem 285:2375-85. 2010
  10. doi Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue
    Zhongxiao Wan
    Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Cell Physiol 299:C1162-70. 2010

Research Grants

  1. DIET INDUCED HYPERINSULINEMIA AND BETA CELL FUNCTION
    Mulchand Patel; Fiscal Year: 2001
  2. REGULATION OF MAMMALIAN DIHYDROLIPOAMIDE DEHYDROGENASE
    Mulchand Patel; Fiscal Year: 2002
  3. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2004
  4. Maternal Hyperinsulinemia and Fetal Programming
    Mulchand Patel; Fiscal Year: 2005
  5. Maternal Hyperinsulinemia and Fetal Programming
    Mulchand Patel; Fiscal Year: 2009
  6. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2000
  7. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 1990
  8. Maternal Hyperinsulinemia and Fetal Programming
    Mulchand S Patel; Fiscal Year: 2010

Scientific Experts

  • THOMAS ROCHE
  • Mulchand Patel
  • M C Sugden
  • Sander Michel Houten
  • Ramy R Attia
  • Marshall B Elam
  • Edwards A Park
  • George A Cook
  • Mark J Holness
  • Bruce C Frier
  • Gustavo Bajotto
  • Lin Piao
  • Felix N Lee
  • Kristína Szántóová
  • David C Wright
  • Sara Connaughton
  • Zhongxiao Wan
  • Karen Bulmer
  • Guixiang Zhao
  • Thomas Cadoudal
  • Christoph M Schummer
  • Yi Zhang
  • Keiko Kusuhara
  • Robert A Harris
  • Young I Kim
  • Rajesh S Savkur
  • Yoshiharu Shimomura
  • Jang H Youn
  • Taro Murakami
  • Yuzo Sato
  • Masaru Nagasaki
  • Ke Ma
  • Woo S Choi
  • Nicholas D Smith
  • Geoffrey F Gibbons
  • Gary D Lopaschuk
  • Stephen L Archer
  • Yong Hu Fang
  • Zhigang Hong
  • Kishan S Parikh
  • John J Ryan
  • Shelby Kutty
  • Erik Morrow
  • Peter T Toth
  • Vaninder K Sidhu
  • L G Korotchkina
  • Anna Veselá
  • Jae Seung Lee
  • Rene L Jacobs
  • Iveta Herichova
  • Michal Zeman
  • Xiong Deng
  • Rachel C Janssen
  • Jacob E Friedman
  • Pragya Sharma
  • Sara Connnaughton
  • Gene C Ness
  • Shulan Song
  • Farhana Chowdhury
  • Lindsey N Sutherland
  • Deon B Williams
  • Melanie Legare
  • Fang Wang
  • Lindsey R Boone
  • A Brianne Thrush
  • James A Richardson
  • Emilie Distel
  • Martin Gerl
  • Guido Haschke
  • Shawn C Burgess
  • Steven A Kliewer
  • Françoise Fouque
  • Werner Kramer
  • Rhonda Bassel-Duby
  • John M Shelton
  • Jean Marc Blouin
  • Norbert Tennagels
  • Kimberly A Rosaaen-Stowe
  • Shuaib Latif
  • Takeshi Inagaki
  • Sylvie Bortoli
  • Dieter Schmoll
  • Andreas W Herling
  • Chantal Benelli
  • John McAnally
  • Sylvie Durant
  • Ulrich Werner
  • Hans Paul Juretschke
  • Nam Ho Jeoung
  • Claude Forest

Detail Information

Publications26

  1. pmc Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex
    M M Bowker-Kinley
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202 5122, USA
    Biochem J 329:191-6. 1998
    ..distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed...
  2. pmc FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate
    Lin Piao
    Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL, USA
    J Mol Med (Berl) 91:333-46. 2013
    ..We hypothesize that FOXO1-mediated PDK4 upregulation causes bioenergetic impairment and RV dysfunction, which can be reversed by dichloroacetate...
  3. ncbi Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase
    L G Korotchkina
    Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214, USA
    J Biol Chem 276:37223-9. 2001
    ..PDKs phosphorylated site 1 and site 2, however, with different rates in phosphate buffer (for site 1, PDK2 > PDK4 approximately PDK1 > PDK3; for site 2, PDK3 > PDK4 > PDK2 > PDK1)...
  4. ncbi Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases
    M S Patel
    Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214, USA
    Exp Mol Med 33:191-7. 2001
    ..Presence of the multiple phosphorylation sites and isoenzymes of PDK is important for the tissue-specific regulation of PDC under different physiological conditions...
  5. ncbi Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy
    Guixiang Zhao
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9041, USA
    Am J Physiol Heart Circ Physiol 294:H936-43. 2008
    ..Hearts from PDK4 transgenic mice have a marked decrease in glucose oxidation and a corresponding increase in fatty acid catabolism...
  6. pmc Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue
    Thomas Cadoudal
    Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche S 747, Universite Paris Descartes, Centre Universitaire des Saints Peres, Paris, France
    Diabetes 57:2272-9. 2008
    ..Thiazolidinediones activate glyceroneogenesis. We studied the regulation by rosiglitazone of PDK2 and PDK4 isoforms and tested the hypothesis that glyceroneogenesis could be controlled by PDK.
  7. doi Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids
    S M Houten
    Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
    Cell Mol Life Sci 66:1283-94. 2009
    ..a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity...
  8. pmc Regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) gene expression by glucocorticoids and insulin
    Sara Connaughton
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA
    Mol Cell Endocrinol 315:159-67. 2010
    ..The expression of the pyruvate dehydrogenase kinase 4 (PDK4) gene is increased in fasting and other conditions associated with the switch from the utilization of glucose to ..
  9. pmc Regulation of pyruvate dehydrogenase kinase 4 (PDK4) by thyroid hormone: role of the peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha)
    Ramy R Attia
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Biol Chem 285:2375-85. 2010
    b>PDK4 (pyruvate dehydrogenase kinase 4) regulates pyruvate oxidation through the phosphorylation and inhibition of the pyruvate dehydrogenase complex (PDC)...
  10. doi Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue
    Zhongxiao Wan
    Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Cell Physiol 299:C1162-70. 2010
    ..A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4)...
  11. doi Effect of phase delay lighting rotation schedule on daily expression of per2, bmal1, rev-erbα, pparα, and pdk4 genes in the heart and liver of Wistar rats
    Kristína Szántóová
    Department of Animal Physiology and Ethology, Comenius University Bratislava, Bratislava, Slovak Republic
    Mol Cell Biochem 348:53-60. 2011
    ..to be a functional interface between circadian clock and metabolism, and its interconnection with rev-erbα and pdk4 was proven...
  12. doi Interactions between the consumption of a high-fat diet and fasting in the regulation of fatty acid oxidation enzyme gene expression: an evaluation of potential mechanisms
    Bruce C Frier
    Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Regul Integr Comp Physiol 300:R212-21. 2011
    ..of medium-chain acyl-CoA dehydrogenase (MCAD), uncoupling protein-3 (UCP3), and pyruvate dehydrogenase kinase 4 (PDK4) in the fed state...
  13. pmc Regulation of pyruvate dehydrogenase kinase 4 (PDK4) by CCAAT/enhancer-binding protein beta (C/EBPbeta)
    Ramy R Attia
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Biol Chem 286:23799-807. 2011
    ..Here, we examined the regulation of Pdk4 gene expression by the CCAAT/enhancer-binding protein β (C/EBPβ)...
  14. ncbi Dysregulated pyruvate dehydrogenase complex in Zucker diabetic fatty rats
    Christoph M Schummer
    Sanofi Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany
    Am J Physiol Endocrinol Metab 294:E88-96. 2008
    ..Pyruvate dehydrogenase kinase-4 (PDK4) protein levels were higher in obese rats, and consequently PDC activity was reduced...
  15. ncbi Calcium signalling in the regulation of PGC-1alpha, PDK4 and HKII mRNA expression
    Keiko Kusuhara
    Copenhagen Muscle Research Centre and Centre of Inflammation and Metabolism, The August Krogh Building, Department of Molecular Biology, University of Copenhagen, Copenhagen Ø, Denmark
    Biol Chem 388:481-8. 2007
    ..and HKII mRNA content approximately two-fold by ionomycin relative to the corresponding controls, whereas the PDK4 mRNA content remained unaffected. Cyclosporin A abolished (p<0.05) and KN-62 reduced (p<0...
  16. pmc Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression
    M C Sugden
    Department of Diabetes, Division of General and Developmental Medicine, St Bartholomew s and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London E1 4NS, U K
    Biochem J 346:651-7. 2000
    ..analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle ..
  17. pmc Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism
    Mark J Holness
    Department of Diabetes and Metabolic Medicine, St Bartholomew s and the Royal London School of Medicine and Dentistry, Medical Sciences Building, Queen Mary, University of London, London E1 4NS, UK
    Biochem J 364:687-94. 2002
    ..potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism...
  18. pmc Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha)
    Mark J Holness
    Department of Diabetes and Metabolic Medicine, Barts and The London, Queen Mary s School of Medicine and Dentistry, University of London, UK
    Biochem J 366:839-46. 2002
    ..receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression...
  19. pmc Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone
    Mark J Holness
    Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, Barts and The London, Queen Mary s School of Medicine and Dentistry, University of London, London, UK
    Biochem J 369:687-95. 2003
    Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC)...
  20. ncbi Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA
    Felix N Lee
    Dept of Physiology and Biophysics, USC Keck School of Medicine, 1333 San Pablo St, MMR 626, Los Angeles, CA 90089 9142, USA
    Am J Physiol Endocrinol Metab 287:E69-74. 2004
    ....
  21. ncbi Downregulation of the skeletal muscle pyruvate dehydrogenase complex in the Otsuka Long-Evans Tokushima Fatty rat both before and after the onset of diabetes mellitus
    Gustavo Bajotto
    Department of Sports Medicine, Graduate School of Medicine, Nagoya University, 464 8601, Japan
    Life Sci 75:2117-30. 2004
    ..These results suggest that concomitant greater PDK4 and less PDP1 expression in skeletal muscle of OLETF rats before the onset of diabetes are responsible for the ..
  22. ncbi Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor
    Rajesh S Savkur
    Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN 46285, USA
    Biochem Biophys Res Commun 329:391-6. 2005
    ..The expression of PDK4 is highly regulated by the glucocorticoid and peroxisome proliferator-activated receptors...
  23. ncbi Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator
    Ke Ma
    Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, 38163, USA
    J Biol Chem 280:29525-32. 2005
    ..There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation ..
  24. ncbi Increased expression of hepatic pyruvate dehydrogenase kinases 2 and 4 in young and middle-aged Otsuka Long-Evans Tokushima Fatty rats: induction by elevated levels of free fatty acids
    Gustavo Bajotto
    Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya 464 8601, Japan
    Metabolism 55:317-23. 2006
    ..In the liver, PDK2 and PDK4 are the most abundant PDK isoforms, which are responsible for inactivation of PDC when glucose availability is ..
  25. ncbi Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states
    Young I Kim
    Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, 1333 San Pablo St, MMR 626, Los Angeles, 90089 9142, USA
    Diabetes 55:2311-7. 2006
    ..In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by ..
  26. ncbi Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer
    T E Roche
    Department of Biochemistry, Kansas State University, Chalmers Hall, Manhattan, KS 66506, USA
    Cell Mol Life Sci 64:830-49. 2007
    ..complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4)...

Research Grants37

  1. DIET INDUCED HYPERINSULINEMIA AND BETA CELL FUNCTION
    Mulchand Patel; Fiscal Year: 2001
    ..This unique rat model has the potential for providing new and significant insight into the "fuel hypothesis" for altered insulin secretory response in response to diet and maternal influences on fetal pancreatic adaptations. ..
  2. REGULATION OF MAMMALIAN DIHYDROLIPOAMIDE DEHYDROGENASE
    Mulchand Patel; Fiscal Year: 2002
    ..abstract_text> ..
  3. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2004
    ..The long term objective is to understand the tissue-specific control of PDC and to delineate the unique properties of kinase isoforms overexpressed in diabetes which inactivates PDC thereby minimize glucose use. ..
  4. Maternal Hyperinsulinemia and Fetal Programming
    Mulchand Patel; Fiscal Year: 2005
    ..Experimental procedures include: artificial rearing of newborn rats, reciprocal embryo transfer, insulin secretion by isolated islets radioimmunoassays, semiquantitative RT-PCR assay, immunohistochemistry and in situ hybridization. ..
  5. Maternal Hyperinsulinemia and Fetal Programming
    Mulchand Patel; Fiscal Year: 2009
    ..Intervention measures proposed for the prevention of the malprogramming effects may lead to development of effective treatment options for curbing the human obesity epidemic. ..
  6. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2000
    ..Aberrant PDC operation is associated with diabetes and obesity. Inborn errors in components cause severe defects. Primary biliary cirrhosis is an autoimmune disease with antibodies to E2 and other PDC subunits. ..
  7. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 1990
    ....
  8. Maternal Hyperinsulinemia and Fetal Programming
    Mulchand S Patel; Fiscal Year: 2010
    ..Intervention measures proposed for the prevention of the malprogramming effects may lead to development of effective treatment options for curbing the human obesity epidemic. ..