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. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2015.09.065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mitigation of depleted uranium-induced mitochondrial damage by ethylmalonic encephalopathy 1 protein via modulation of hydrogen sulfide and glutathione pathways.
Arch Toxicol
December 2024
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
Depleted uranium (DU) is a byproduct of uranium enrichment, which can cause heavy-metal toxicity and radiation toxicity as well as serious damage to the kidneys. However, the mechanism of renal injury induced by DU is still unclear. This study aimed to explore the role of ethylmalonic encephalopathy 1 (ETHE1) in DU-induced mitochondrial dysfunction and elucidate the underlying mechanisms.
View Article and Find Full Text PDFReduction in Renal Heme Oxygenase-1 Is Associated with an Aggravation of Kidney Injury in Shiga Toxin-Induced Murine Hemolytic-Uremic Syndrome.
Toxins (Basel)
December 2024
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.
Hemolytic-uremic syndrome (HUS) is a systemic complication of an infection with Shiga toxin (Stx)-producing enterohemorrhagic , primarily leading to acute kidney injury (AKI) and microangiopathic hemolytic anemia. Although free heme has been found to aggravate renal damage in hemolytic diseases, the relevance of the heme-degrading enzyme heme oxygenase-1 (HO-1, encoded by ) in HUS has not yet been investigated. We hypothesized that HO-1 also important in acute phase responses in damage and inflammation, contributes to renal pathogenesis in HUS.
View Article and Find Full Text PDFMettl3-Mediated m6A Modification is Essential for Visual Function and Retinal Photoreceptor Survival.
Invest Ophthalmol Vis Sci
December 2024
The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Purpose: N6-methyladenosine (m6A) modification, one of the most common epigenetic modifications in eukaryotic mRNA, has been shown to play a role in the development and function of the mammalian nervous system by regulating the biological fate of mRNA. METTL3, the catalytically active component of the m6A methyltransferase complex, has been shown to be essential in development of in the retina. However, its role in the mature retina remains elusive.
View Article and Find Full Text PDFUntargeted Metabolomics Reveals Dysregulation of Glycine- and Serine-Coupled Metabolic Pathways in an ALDH1L1-Dependent Manner In Vivo.
Metabolites
December 2024
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
ALDH1L1 plays a crucial role in folate metabolism, regulating the flow of one-carbon groups through the conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO in a NADP-dependent reaction. The downregulation of ALDH1L1 promotes malignant tumor growth, and silencing of ALDH1L1 is commonly observed in many cancers. In a previous study, knockout (KO) mice were found to have an altered liver metabotype, including significant alterations in glycine and serine.
View Article and Find Full Text PDFLoss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection.
J Virol
December 2024
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!