Genomes and Genes
Gene Symbol: Hmgcr
Description: 3-hydroxy-3-methylglutaryl-CoA reductase
Alias: 3H3M, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG-CoA reductase
- 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. ..
- Gillespie J, Hardie D. Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes. FEBS Lett. 1992;306:59-62 pubmed
- MAMMEN A, Chung T, Christopher Stine L, Rosen P, Rosen A, Doering K, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63:713-21 pubmed publisher..was confirmed by immunoprecipitation of in vitro-translated 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein. HMGCR expression in muscle was analyzed by immunofluorescence...
- Luskey K, Stevens B. Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985;260:10271-7 pubmed
- 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
- Kumagai Y, Sekimoto M, Okamoto M, Kurita R, Kojima M, Degawa M. Involvement of hepatic IL-1 in the strain-dependent sex differences in serum total cholesterol levels in rats. Biol Pharm Bull. 2014;37:654-8 pubmed
- Segatto M, Di Giovanni A, Marino M, Pallottini V. Analysis of the protein network of cholesterol homeostasis in different brain regions: an age and sex dependent perspective. J Cell Physiol. 2013;228:1561-7 pubmed publisher..Some of these differences could be at the root of marked gender disparities observed in clinical disease incidence, manifestation, and prognosis. ..
- Pallottini V, Martini C, Bassi A, Romano P, Nanni G, Trentalance A. Rat HMGCoA reductase activation in thioacetamide-induced liver injury is related to an increased reactive oxygen species content. J Hepatol. 2006;44:368-74 pubmed..It is suggested that reducing the levels of reactive oxygen species may improve the altered lipid profile found in liver injury. ..
- Yamazaki H, Suzuki M, Aoki T, Morikawa S, Maejima T, Sato F, et al. Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ubiquinone levels in rat skeletal muscle and heart: relationship to cytotoxicity and inhibitory activity for cholesterol synthesis in human skeletal muscle cells. J Atheroscler Thromb. 2006;13:295-307 pubmed..We found that cerivastatin showed the most potent cytotoxicity in HSkMCs and strongly lowered ubiquinone levels in the rat heart. ..
- 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. ..
- 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...
- Chen C, Cheng H. A rice bran oil diet increases LDL-receptor and HMG-CoA reductase mRNA expressions and insulin sensitivity in rats with streptozotocin/nicotinamide-induced type 2 diabetes. J Nutr. 2006;136:1472-6 pubmed..The high contents of gamma-oryzanol and gamma-tocotrienol in RBO can lead to increased fecal neutral sterol and bile acid excretion, via upregulation of cholesterol synthesis and catabolism. ..
- 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. ..
- Stakhneva E, Vavilin V, Ragino Y, Safronova O, Shintyapina A, Ivanova M. Effects of simvaglyzin and atorvaglyzin on the expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase in rat liver. Bull Exp Biol Med. 2013;156:63-5 pubmed..Activity of this enzyme decreased by 46% in rats treated with atorvaglyzin. The amount of messenger RNA in these groups significantly increased as compared to control group (untreated animals). ..
- 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. ..
- Istvan E, Palnitkar M, Buchanan S, Deisenhofer J. Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000;19:819-30 pubmed..The active site architecture of human HMGR is different from that of bacterial HMGR; this may explain why binding of HMGR inhibitors to bacterial HMGRs has not been reported. ..
- Ness G, Holland R, Lopez D. Selective compensatory induction of hepatic HMG-CoA reductase in response to inhibition of cholesterol absorption. Exp Biol Med (Maywood). 2006;231:559-65 pubmed..This indicates that ezetimibe should be most effective in lowering serum cholesterol levels in people with low rates of cholesterol synthesis/high rates of cholesterol absorption. ..
- Rombouts K, Kisanga E, Hellemans K, Wielant A, Schuppan D, Geerts A. Effect of HMG-CoA reductase inhibitors on proliferation and protein synthesis by rat hepatic stellate cells. J Hepatol. 2003;38:564-72 pubmed..Our data showed that lovastatin and simvastatin inhibited HSC proliferation and collagen steady state levels by mechanisms independent of their lipid reducing activities. ..
- Prasad G, Kim S, Huang M, Nash M, Zaltzman J, Fenton S, et al. Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins). Am J Transplant. 2004;4:1897-903 pubmed..02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation. ..
- Clarke P, Hardie D. Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver. EMBO J. 1990;9:2439-46 pubmed..We have also identified by amino acid sequencing the N-terminus of the catalytic fragment, which corresponds to residue 423 of the human enzyme. ..
- Yasuda H, Yuen P, Hu X, Zhou H, Star R. Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects. Kidney Int. 2006;69:1535-42 pubmed..Simvastatin improved sepsis-induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect. ..
- Ucak A, Onan B, Guler A, Sahin M, Kılıçkaya O, Oztas E, et al. Rosuvastatin, a new generation 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, reduces ischemia/reperfusion-induced spinal cord tissue injury in rats. Ann Vasc Surg. 2011;25:686-95 pubmed publisher..RSV administration before spinal cord ischemia reduces spinal cord tissue injury by increasing antioxidant enzyme levels and may reduce the incidence of associated neurological dysfunction. ..
- Boone L, Niesen M, Jaroszeski M, Ness G. In vivo identification of promoter elements and transcription factors mediating activation of hepatic HMG-CoA reductase by T3. Biochem Biophys Res Commun. 2009;385:466-71 pubmed publisher..These data provide in vivo evidence for functional roles for USF-2, SREBP-2, and NF-Y in mediating the T3-induction of hepatic HMGR transcription. ..
- Song B, DeBose Boyd R. Ubiquitination of 3-hydroxy-3-methylglutaryl-CoA reductase in permeabilized cells mediated by cytosolic E1 and a putative membrane-bound ubiquitin ligase. J Biol Chem. 2004;279:28798-806 pubmed
- Ying S, Sun Y, Liu X, An C, Gao Y. Effect of ScrF I polymorphism in the 2nd intron of the HMGCR gene on lipid-lowering response to simvastatin in Chinese diabetic patients. Biochem Biophys Res Commun. 2007;363:395-8 pubmedTo investigate whether ScrF I polymorphism in the 2nd intron of the HMG-COA reductase gene (HMGCR) influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor,..
- Pallottini V, Martini C, Cavallini G, Bergamini E, Mustard K, Hardie D, et al. Age-related HMG-CoA reductase deregulation depends on ROS-induced p38 activation. Mech Ageing Dev. 2007;128:688-95 pubmed..Moreover, H(2)O(2)-stimulated HepG2 cell line shows that the ROS effect on the HMG-CoAR dephosphorylation is mediated by the activation of p38/MAPK pathway. ..
- Ness G, Edelman J, Brooks P. Involvement of tristetraprolin in transcriptional activation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase by insulin. Biochem Biophys Res Commun. 2012;420:178-82 pubmed publisher..In comparison, siRNA to AU RNA binding protein/enoyl coenzyme A hydratase (AUH) had no effect. These findings indicate a role for TTP in the insulin-mediated activation of hepatic HMGR transcription. ..
- 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. ..
- Tristano A, Castejon A, Castro A, Cubeddu L. Effects of statin treatment and withdrawal on angiotensin II-induced phosphorylation of p38 MAPK and ERK1/2 in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 2007;353:11-7 pubmed..Our results suggest that statins modulate AII effects in VSMC, and that transient increases in AII effects mediated via the MAPK pathway may play a role in the vascular dysfunction associated with statin withdrawal. ..
- Chen X, Besson V, Beziaud T, Plotkine M, Marchand Leroux C. Combination therapy with fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, and simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on experimental traumatic brain injury. J Pharmacol Exp Ther. 2008;326:966-74 pubmed publisher..Thus, these results may have important therapeutic significance for the treatment of TBI. ..
- Wolozin B, Wang S, Li N, Lee A, Lee T, Kazis L. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 2007;5:20 pubmed
- Ostroukhova M, Kouides R, Friedman E. The effect of statin therapy on allergic patients with asthma. Ann Allergy Asthma Immunol. 2009;103:463-8 pubmed publisher..003). This preliminary study demonstrated that patients with asthma who received statins had a worse clinical course than controls. Given the prevalence of both statin use and asthma, further research is needed. ..
- Zhang L, Zhang Z, Ding G, Jiang Q, Liu X, Meng H, et al. Multitargeted effects of statin-enhanced thrombolytic therapy for stroke with recombinant human tissue-type plasminogen activator in the rat. Circulation. 2005;112:3486-94 pubmed
- Pallottini V, Martini C, Cavallini G, Donati A, Bergamini E, Notarnicola M, et al. Modified HMG-CoA reductase and LDLr regulation is deeply involved in age-related hypercholesterolemia. J Cell Biochem. 2006;98:1044-53 pubmed..The SREBP-2 in particular seems to be committed in multiple way to gene transcription. The obtained data represent a good contribution to explain the age-related hypercholesterolemia. ..
- 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. ..
- Harry R, Gegg M, Hankey D, Zambarakji H, Pryce G, Baker D, et al. Suppression of autoimmune retinal disease by lovastatin does not require Th2 cytokine induction. J Immunol. 2005;174:2327-2335 pubmed..These data highlight the potential differential activity of statins in different inflammatory conditions and their possible therapeutic use for the treatment of human posterior uveitis. ..
- Rung E, Friberg P, Shao R, Larsson D, Nielsen E, Svensson P, et al. Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro. Biol Reprod. 2005;72:538-45 pubmed..These results show that PR antagonists reduce cholesterol synthesis in periovulatory granulosa cells and that cholesterol synthesis is important for granulosa cell survival. ..
- Trapani L, Violo F, Pallottini V. Hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A reductase regulation in aged female rats. Exp Gerontol. 2010;45:119-28 pubmed publisher..These findings highlight the correlation between estrogen and HMGR short-term regulation, and suggest the presence of another mechanism underlying the protective role of estrogen in age-related diseases. ..
- Yamagata T, Kinoshita K, Nozaki Y, Sugiyama M, Ikoma S, Funauchi M. Effects of pravastatin in murine collagen-induced arthritis. Rheumatol Int. 2007;27:631-9 pubmed..Meanwhile, adverse reactions of pravastatin, such as peritonitis, were not detected. Pravastatin may have good prospects for treating some anti-inflammatory effects on human rheumatoid arthritis. ..
- Miyahara S, Kiryu J, Yamashiro K, Miyamoto K, Hirose F, Tamura H, et al. Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes. Am J Pathol. 2004;164:1697-706 pubmed..Simvastatin may thus be useful in the prevention of diabetic retinopathy. ..
- Edwards P, Kempner E, Lan S, Erickson S. Functional size of rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase as determined by radiation inactivation. J Biol Chem. 1985;260:10278-82 pubmed..The simplest interpretation of these results is that rat liver 3-hydroxy-3-methylglutaryl-CoA reductase in situ is a noncovalently linked dimer of the Mr = 97,200 enzyme subunit. ..
- Waehre T, Damås J, Gullestad L, Holm A, Pedersen T, Arnesen K, et al. Hydroxymethylglutaryl coenzyme a reductase inhibitors down-regulate chemokines and chemokine receptors in patients with coronary artery disease. J Am Coll Cardiol. 2003;41:1460-7 pubmed..This study demonstrates a down-regulatory effect of statins on the chemokine network in CAD patients, possibly contributing to the beneficial effects of statins in this disorder. ..
- 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. ..
- Sarkey J, Richards M, Stubbs E. Lovastatin attenuates nerve injury in an animal model of Guillain-Barré syndrome. J Neurochem. 2007;100:1265-77 pubmed..Together, these data demonstrate that a short-term course of lovastatin attenuates the development and progression of EAN in Lewis rats by limiting the proliferation and migration of autoreactive leukocytes. ..
- Abe M, Toyohara T, Ishii A, Suzuki T, Noguchi N, Akiyama Y, et al. The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides. Drug Metab Pharmacokinet. 2010;25:274-82 pubmed..In addition, insulin secretion from isolated islets was enhanced by pravastatin. These data suggest that pravastatin has pleiotropic effects on islets through membrane transport under high fat/glucose conditions. ..
- Lagor W, Heller R, de Groh E, Ness G. Functional analysis of the hepatic HMG-CoA reductase promoter by in vivo electroporation. Exp Biol Med (Maywood). 2007;232:353-61 pubmed..We also conclude that in vivo electroporation is a convenient and powerful technique for the analysis of promoter elements in the livers of live animals. ..
- Li G, Larson E, Sonnen J, Shofer J, Petrie E, Schantz A, et al. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology. 2007;69:878-85 pubmed..Additional study is needed to examine whether statin use may be causally related to decreased development of Alzheimer disease-related neuropathologic changes. ..