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
- Ness G, Holland R. Degradation of HMG-CoA reductase in rat liver is cholesterol and ubiquitin independent. FEBS Lett. 2005;579:3126-30 pubmed..The results indicate that in liver, neither the rate of reductase protein degradation nor the ubiquitin-proteasome system appear to play roles in mediating changes in HMG-CoA reductase protein levels in response to dietary cholesterol. ..
- Kilic U, Bassetti C, Kilic E, Xing H, Wang Z, Hermann D. Post-ischemic delivery of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin protects against focal cerebral ischemia in mice via inhibition of extracellular-regulated kinase-1/-2. Neuroscience. 2005;134:901-6 pubmed..Our results indicate that rosuvastatin may have utility not only as stroke prophylaxis but also as acute therapy inhibiting executive cell death pathways. ..
- Levy E, Brunet S, Alvarez F, Seidman E, Bouchard G, Escobar E, et al. Abnormal hepatobiliary and circulating lipid metabolism in the Long-Evans Cinnamon rat model of Wilson's disease. Life Sci. 2007;80:1472-83 pubmed..Our data emphasize the crucial role of copper balance in hepatic sterol homeostasis and lipoprotein metabolism in LEC rats. Additional studies are needed to delineate the mechanisms of these disorders. ..
- McPherson R, Bedard J, Connelly P, Curnew G, Davignon J, Echenberg D, et al. Comparison of the short-term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. Clin Ther. 1992;14:276-91 pubmed..The frequency of overall side effects, including central nervous system-related symptoms and headache, was similar and low in all groups. ..
- Pallottini V, Montanari L, Cavallini G, Bergamini E, Gori Z, Trentalance A. Mechanisms underlying the impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in aged rat liver. Mech Ageing Dev. 2004;125:633-9 pubmed..These findings support the hypothesis that a different arrangement of the HMG-CoA reductase membrane domain in aged rats is a cause of reductase deregulation. ..
- Waterham H. Defects of cholesterol biosynthesis. FEBS Lett. 2006;580:5442-9 pubmed..The etiology of the underlying pathophysiology may involve multiple affected processes due to lowered cholesterol and/or the elevated, teratogenic levels of the intermediate sterol precursors. ..
- Lee J, Lee J, Jung E, Cho J, Park D. Artemisinic acid inhibits melanogenesis through downregulation of C/EBP ?-dependent expression of HMG-CoA reductase gene. Food Chem Toxicol. 2013;51:225-30 pubmed publisher..indicate that the inhibition of melanogenesis by artemisinic acid occurs through reduced expression of the HMG CoA reductase gene, which is mediated by C/EBP ? inhibition and suggest that artemisinic acid may be useful as a ..
- Neuvonen P, Backman J, Niemi M. Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin. Clin Pharmacokinet. 2008;47:463-74 pubmed..On the pharmacokinetic basis, fluvastatin and pravastatin can be better choices than simvastatin or lovastatin for an OTC statin. ..
- Visavadiya N, Narasimhacharya A. Ameliorative effect of Chlorophytum borivilianum root on lipid metabolism in hyperlipaemic rats. Clin Exp Pharmacol Physiol. 2007;34:244-9 pubmed..7. Administration of C. borivilianum root powder also increased the activities of anti-oxidant enzymes and vitamin C levels, which may have enhanced the anti-oxidant capacity of the liver. ..
- 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. ..