Hmgcr

Summary

Gene Symbol: Hmgcr
Description: 3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Alias: HMG-CoAR, Red, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 3-hydroxy-3-methylglutaryl-CoA reductase, HMG-CoA reductase
Species: mouse
Products:     Hmgcr

Top Publications

  1. Ohashi K, Osuga J, Tozawa R, Kitamine T, Yagyu H, Sekiya M, et al. Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. J Biol Chem. 2003;278:42936-41 pubmed
    ..We used gene targeting to knock out the mouse HMG-CoA reductase gene. The heterozygous mutant mice (Hmgcr+/-) appeared normal in their development and gross anatomy and were fertile...
  2. Naito M, Bomsztyk K, Zager R. Renal ischemia-induced cholesterol loading: transcription factor recruitment and chromatin remodeling along the HMG CoA reductase gene. Am J Pathol. 2009;174:54-62 pubmed publisher
    ..However, the factors during acute kidney injury that regulate HMG CoA reductase (HMGCR) activity, the rate-limiting step in cholesterol synthesis, have not been defined...
  3. Marijanovic Z, Laubner D, Moller G, Gege C, Husen B, Adamski J, et al. Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis. Mol Endocrinol. 2003;17:1715-25 pubmed
    ..In its function as the 3-ketosteroid reductase of cholesterol biosynthesis, HSD17B7 is a novel candidate for inborn errors of cholesterol metabolism. ..
  4. Cunningham D, DeBarber A, Bir N, Binkley L, Merkens L, Steiner R, et al. Analysis of hedgehog signaling in cerebellar granule cell precursors in a conditional Nsdhl allele demonstrates an essential role for cholesterol in postnatal CNS development. Hum Mol Genet. 2015;24:2808-25 pubmed publisher
    ..They further emphasize the complex ramifications of cholesterogenic enzyme deficiency on cellular metabolism. ..
  5. Hasegawa S, Kume H, Iinuma S, Yamasaki M, Takahashi N, Fukui T. Acetoacetyl-CoA synthetase is essential for normal neuronal development. Biochem Biophys Res Commun. 2012;427:398-403 pubmed publisher
    ..These results suggest that AACS is regulated by SREBP-2 and involves in the normal development of neurons. ..
  6. Cho S, Jun H, Lee J, Jia Y, Kim K, Lee S. Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms. FEBS Lett. 2011;585:3289-96 pubmed publisher
    ..These findings suggest that food molecules with a pleasant scent could exert beneficial metabolic effects through multiple mechanisms. ..
  7. Watanabe M, Ayugase J. Effects of buckwheat sprouts on plasma and hepatic parameters in type 2 diabetic db/db mice. J Food Sci. 2010;75:H294-9 pubmed publisher
    ..It was deduced that excretion of bile acids in feces by feeding the BS diet would contribute to the suppression of the cholesterol concentration in the plasma and liver tissues of mice. ..
  8. Plump A, Erickson S, Weng W, Partin J, Breslow J, Williams D. Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production. J Clin Invest. 1996;97:2660-71 pubmed
  9. Hanaka S, Abe T, Itakura H, Matsumoto A. Gene expression related to cholesterol metabolism in mouse brain during development. Brain Dev. 2000;22:321-6 pubmed

More Information

Publications53

  1. Beigneux A, Kosinski C, Gavino B, Horton J, Skarnes W, Young S. ATP-citrate lyase deficiency in the mouse. J Biol Chem. 2004;279:9557-64 pubmed
    ..The Acly knockout allele is useful for identifying cell types with a high demand for acetyl-CoA synthesis. ..
  2. Munkacsi A, Hammond N, Schneider R, Senanayake D, Higaki K, Lagutin K, et al. Normalization of Hepatic Homeostasis in the Npc1nmf164 Mouse Model of Niemann-Pick Type C Disease Treated with the Histone Deacetylase Inhibitor Vorinostat. J Biol Chem. 2017;292:4395-4410 pubmed publisher
    ..These results suggest that HDAC inhibitors have utility to treat visceral NP-C disease. However, it is clear that improved blood-brain barrier penetration will be required to alleviate the neurological symptoms of human NP-C disease. ..
  3. Shirai N, Suzuki H. Effect of docosahexaenoic acid on brain 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in male ICR mice. J Nutr Biochem. 2007;18:488-94 pubmed
    ..The DHA percentages of brain and liver microsomal fractions increased with the intake of DHA-EE in adult and aged mice. These results suggest that DHA may enhance brain HMG-CoA reductase activity in aged mice. ..
  4. Schiefelbein D, Goren I, Fisslthaler B, Schmidt H, Geisslinger G, Pfeilschifter J, et al. Biphasic regulation of HMG-CoA reductase expression and activity during wound healing and its functional role in the control of keratinocyte angiogenic and proliferative responses. J Biol Chem. 2008;283:15479-90 pubmed publisher
  5. Korade Z, Kenchappa R, Mirnics K, Carter B. NRIF is a regulator of neuronal cholesterol biosynthesis genes. J Mol Neurosci. 2009;38:152-8 pubmed publisher
    ..decreased the mRNA for two main cholesterogenic enzymes, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr; EC 2.3.3.10) and 7-dehydrocholesterol reductase (Dhcr7; EC 1.3.1.21)...
  6. Hayek T, Kaplan M, Kerry R, Aviram M. Macrophage NADPH oxidase activation, impaired cholesterol fluxes, and increased cholesterol biosynthesis in diabetic mice: a stimulatory role for D-glucose. Atherosclerosis. 2007;195:277-86 pubmed
    ..The above mechanisms in diabetic mice could be the result of the effect of high D-glucose on macrophages. ..
  7. Wu M, Cohen D. Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice. Am J Physiol Gastrointest Liver Physiol. 2005;289:G456-61 pubmed
    ..We speculate that regulation of cholesterol homeostasis is a physiological function of PC-TP in liver, which can be overcome with a cholesterol-rich lithogenic diet. ..
  8. Lu H, Talbot S, Robertson K, Watterson S, Forster T, Roy D, et al. Rapid proteasomal elimination of 3-hydroxy-3-methylglutaryl-CoA reductase by interferon-γ in primary macrophages requires endogenous 25-hydroxycholesterol synthesis. Steroids. 2015;99:219-29 pubmed publisher
    ..IFN controls the first regulated step in the mevalonate-sterol pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), through the synthesis of 25-Hydroxycholesterol (25-HC) from cholesterol by the IFN-inducible Cholesterol-25-..
  9. Hwa J, Zollman S, Warden C, Taylor B, Edwards P, Fogelman A, et al. Genetic and dietary interactions in the regulation of HMG-CoA reductase gene expression. J Lipid Res. 1992;33:711-25 pubmed
    ..The variation provides a striking example, at the molecular level, of the importance of dietary-genetic interactions in the control of cholesterol metabolism. ..
  10. Lacher S, Bruttger J, Kalt B, Berthelet J, Rajalingam K, Wörtge S, et al. HMG-CoA reductase promotes protein prenylation and therefore is indispensible for T-cell survival. Cell Death Dis. 2017;8:e2824 pubmed publisher
    ..cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR)...
  11. Sundaresan S, Yang Feng T, Francke U. Genes for HMG-CoA reductase and serotonin 1a receptor are on mouse chromosome 13. Somat Cell Mol Genet. 1989;15:465-9 pubmed
    ..The human gene (HMGCR) has been assigned to the q13.3-q14 region of chromosome 5 (HSA5)...
  12. Engelking L, Liang G, Hammer R, Takaishi K, Kuriyama H, Evers B, et al. Schoenheimer effect explained--feedback regulation of cholesterol synthesis in mice mediated by Insig proteins. J Clin Invest. 2005;115:2489-98 pubmed
    ..These studies indicate that the essential elements of the regulatory pathway for lipid synthesis function in liver as they do in cultured cells. ..
  13. Hogenboom S, Romeijn G, Houten S, Baes M, Wanders R, Waterham H. Absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis. J Lipid Res. 2002;43:90-8 pubmed
    ..Our data provide an explanation for the conflicting findings in the literature and show that great care should be taken in the interpretation of data obtained in postmortem material. ..
  14. Shimano H, Horton J, Hammer R, Shimomura I, Brown M, Goldstein J. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest. 1996;98:1575-84 pubmed
    ..The mRNAs encoding 3-hydroxy-3-methylglutaryl CoA (HMG CoA) synthase, HMG CoA reductase, squalene synthase, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1 were all ..
  15. Welch C, Bretschger S, Wen P, Mehrabian M, Latib N, Fruchart Najib J, et al. Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain. Physiol Genomics. 2004;17:48-59 pubmed
    ..003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans. ..
  16. Buchovecky C, Turley S, Brown H, Kyle S, McDonald J, Liu B, et al. A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome. Nat Genet. 2013;45:1013-20 pubmed publisher
    ..Our genetic screen therefore points to cholesterol homeostasis as a potential target for the treatment of patients with Rett syndrome. ..
  17. Tsai Y, Leichner G, Pearce M, Wilson G, Wojcikiewicz R, Roitelman J, et al. Differential regulation of HMG-CoA reductase and Insig-1 by enzymes of the ubiquitin-proteasome system. Mol Biol Cell. 2012;23:4484-94 pubmed publisher
    ..Our results suggest a need for additional studies before definitive mechanistic conclusions are drawn that might set the stage for development of drugs to manipulate gp78 function in metabolic disorders. ..
  18. Sonawane P, Sahu B, Sasi B, Geedi P, Lenka G, Mahapatra N. Functional promoter polymorphisms govern differential expression of HMG-CoA reductase gene in mouse models of essential hypertension. PLoS ONE. 2011;6:e16661 pubmed publisher
    3-Hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase gene (Hmgcr) is a susceptibility gene for essential hypertension...
  19. Patra D, DeLassus E, Liang G, Sandell L. Cartilage-specific ablation of site-1 protease in mice results in the endoplasmic reticulum entrapment of type IIb procollagen and down-regulation of cholesterol and lipid homeostasis. PLoS ONE. 2014;9:e105674 pubmed publisher
    ..This role appears not to be related to lipid pathways or other current known functions of S1P and is likely dependent on additional, yet unknown, S1P substrates in chondrocytes. ..
  20. Goodrum J, Bouldin T, Zhang S, Maeda N, Popko B. Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-I in mice. J Neurochem. 1995;64:408-16 pubmed
    ..These data suggest that there is considerable redundancy in the process of cholesterol reutilization within nerve, and that apolipoproteins other than apolipoproteins E and A-I may be involved in the recycling of myelin cholesterol. ..
  21. Nagashima S, Yagyu H, Ohashi K, Tazoe F, Takahashi M, Ohshiro T, et al. Liver-specific deletion of 3-hydroxy-3-methylglutaryl coenzyme A reductase causes hepatic steatosis and death. Arterioscler Thromb Vasc Biol. 2012;32:1824-31 pubmed publisher
    3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) catalyzes the rate-limiting step in cholesterol biosynthesis and has proven to be an effective target of lipid-lowering drugs, statins...
  22. Rub A, Dey R, Jadhav M, Kamat R, Chakkaramakkil S, Majumdar S, et al. Cholesterol depletion associated with Leishmania major infection alters macrophage CD40 signalosome composition and effector function. Nat Immunol. 2009;10:273-80 pubmed publisher
    ..Thus, cholesterol depletion might represent an immune-evasion strategy used by L. major. ..
  23. Ying Z, Desikan R, Xu X, Maiseyeu A, Liu C, Sun Q, et al. Modified methylenedioxyphenol analogs lower LDL cholesterol through induction of LDL receptor expression. J Lipid Res. 2012;53:879-87 pubmed publisher
    ..INV-403 lowered plasma LDL cholesterol levels through LDLR upregulation. These results indicate a role for small molecule approaches other than statins for lowering LDL cholesterol. ..
  24. Bojanic D, Tarr P, Gale G, Smith D, Bok D, Chen B, et al. Differential expression and function of ABCG1 and ABCG4 during development and aging. J Lipid Res. 2010;51:169-81 pubmed publisher
    ..Finally, behavioral tests show that Abcg4(-/-) mice have a general deficit in associative fear memory. Together, these data indicate that loss of ABCG1 and/or ABCG4 from the CNS results in changes in metabolic pathways and in behavior...
  25. Vergnes L, Chin R, de Aguiar Vallim T, Fong L, Osborne T, Young S, et al. SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. J Lipid Res. 2016;57:410-21 pubmed publisher
    ..Reduced expression of SREBP-2 from the hypomorphic allele leads to early death in females and reduced cholesterol content in the liver, but not in adipose tissue. ..
  26. Ding J, Jiang D, Kurczy M, Nalepka J, Dudley B, Merkel E, et al. Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse. BMC Dev Biol. 2008;8:120 pubmed publisher
    ..Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR) resulting in germ cell survival and migration defects...
  27. Hwang S, Nguyen A, Jo Y, Engelking L, Brugarolas J, DeBose Boyd R. Hypoxia-inducible factor 1? activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver. J Biol Chem. 2017;292:9382-9393 pubmed publisher
    ..endoplasmic reticulum-associated degradation of the rate-limiting enzyme in the pathway, HMG-CoA reductase (HMGCR)...
  28. Patel D, Knight B, Wiggins D, Humphreys S, Gibbons G. Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice. J Lipid Res. 2001;42:328-37 pubmed
    ..Patel, D. D., B. L. Knight, D. Wiggins, S. M. Humphreys, and G. F. Gibbons. Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice. J. Lipid Res. 2001. 42: 328--337. ..
  29. Kovacs W, Faust P, Keller G, Krisans S. Purification of brain peroxisomes and localization of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Eur J Biochem. 2001;268:4850-9 pubmed
    ..In addition, we show by analytical subcellular fractionation and immunoelectron microscopy that HMG-CoA reductase protein and activity are localized both in the ER and peroxisomes in the CNS. ..
  30. Osaki Y, Nakagawa Y, Miyahara S, Iwasaki H, Ishii A, Matsuzaka T, et al. Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy. Biochem Biophys Res Commun. 2015;466:536-40 pubmed publisher
    HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol...
  31. Langston T, Hylemon P, Grogan W. Over-expression of hepatic neutral cytosolic cholesteryl ester hydrolase in mice increases free cholesterol and reduces expression of HMG-CoAR, CYP27, and CYP7A1. Lipids. 2005;40:31-8 pubmed
    ..These results demonstrate elevation of FC and depletion of cholesteryl esters by over-expression of hncCEH, which were resistant to compensatory responses by other enzymes of cholesterol homeostasis. ..
  32. Fonseca T, Fernandes G, McAninch E, Bocco B, Abdalla S, Ribeiro M, et al. Perinatal deiodinase 2 expression in hepatocytes defines epigenetic susceptibility to liver steatosis and obesity. Proc Natl Acad Sci U S A. 2015;112:14018-23 pubmed publisher
    ..The resulting phenotype of the adult ALB-D2KO mouse is dramatic, with greatly reduced susceptibility to diet-induced steatosis, hypertriglyceridemia, and obesity. ..
  33. Bell J, Noveen A, Liu Y, Ma L, Dobias S, Kundu R, et al. Genomic structure, chromosomal location, and evolution of the mouse Hox 8 gene. Genomics. 1993;16:123-31 pubmed
    ..abstract truncated at 250 words) ..
  34. Zhang X, Song Y, Feng M, Zhou X, Lu Y, Gao L, et al. Thyroid-stimulating hormone decreases HMG-CoA reductase phosphorylation via AMP-activated protein kinase in the liver. J Lipid Res. 2015;56:963-71 pubmed publisher
    Cholesterol homeostasis is strictly regulated through the modulation of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis. Phosphorylation of HMGCR inactivates it and dephosphorylation activates it...
  35. Chen Y, Ku H, Zhao L, Wheeler D, Li L, Li Q, et al. Inflammatory stress induces statin resistance by disrupting 3-hydroxy-3-methylglutaryl-CoA reductase feedback regulation. Arterioscler Thromb Vasc Biol. 2014;34:365-76 pubmed publisher
    ..Increased cholesterol synthesis mediated by HMGCoA-R under inflammatory stress may be one of the mechanisms for intracellular lipid accumulation and statin resistance. ..
  36. Hyogo H, Roy S, Paigen B, Cohen D. Leptin promotes biliary cholesterol elimination during weight loss in ob/ob mice by regulating the enterohepatic circulation of bile salts. J Biol Chem. 2002;277:34117-24 pubmed
    ..Cholesterol gallstone formation during weight loss in ob/ob mice appears to represent a pathologic consequence of an adaptive response that prevents absorption of biliary and dietary cholesterol. ..
  37. Yubero P, Hondares E, Carmona M, Rossell M, Gonzalez F, Iglesias R, et al. The developmental regulation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression in the liver is partially dissociated from the control of gluconeogenesis and lipid catabolism. Endocrinology. 2004;145:4268-77 pubmed
  38. Helmberg A, Fassler R, Geley S, Johrer K, Kroemer G, Bock G, et al. Glucocorticoid-regulated gene expression in the immune system. Analysis of glucocorticoid-regulated transcripts from the mouse macrophage-like cell line P388D1. J Immunol. 1990;145:4332-7 pubmed
    ..Our results raise the possibility that the immunosuppressive activity of glucocorticoids might be mediated, in part, by regulating the expression of the above immunoregulatory proteins. ..
  39. Manitsopoulos N, Orfanos S, Kotanidou A, Nikitopoulou I, Siempos I, Magkou C, et al. Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation. Respir Res. 2015;16:24 pubmed publisher
    ..High-dose simvastatin prevents experimental hyperinflation lung injury by angioprotective and anti-inflammatory effects. ..
  40. Plump A, Azrolan N, Odaka H, Wu L, Jiang X, Tall A, et al. ApoA-I knockout mice: characterization of HDL metabolism in homozygotes and identification of a post-RNA mechanism of apoA-I up-regulation in heterozygotes. J Lipid Res. 1997;38:1033-47 pubmed
    ..In the apoA-I knockout mouse model it appears that low HDL levels create a new steady state in which decreased cholesterol is delivered to both peripheral tissues and the liver. ..
  41. Myöhänen S, Wahlfors J, Alhonen L, Janne J. Nucleotide sequence of mouse spermidine synthase cDNA. DNA Seq. 1994;4:343-6 pubmed
    ..The open reading frame encoded a polypeptide of 302 amino acids, displaying 95% similarity to human and 33% similarity to E. coli spermidine synthase. The 3' flanking region contained an unusual polyadenylation signal AATACA. ..
  42. Hwang S, Hartman I, Calhoun L, Garland K, Young G, Mitsche M, et al. Contribution of Accelerated Degradation to Feedback Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Cholesterol Metabolism in the Liver. J Biol Chem. 2016;291:13479-94 pubmed publisher
    ..endoplasmic reticulum membranes stimulates the ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which catalyzes a rate-limiting step in synthesis of cholesterol...
  43. Raben N, Jatkar T, Lee A, Lu N, Dwivedi S, Nagaraju K, et al. Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme. Mol Ther. 2002;6:601-8 pubmed
    ..The results demonstrate that complete reversal of pathology in skeletal muscle or long-affected heart muscle will require much more enzyme than previously expected or a different approach. ..
  44. Shin S, Vogt E, Jimenez Movilla M, Baibakov B, Dean J. Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice. Nat Commun. 2017;8:1643 pubmed publisher
    ..Thus, the N-terminus of DPPA3 has a significant role in cytoplasmic vesicular trafficking in addition to its previously reported nuclear function. ..