Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins.
The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most effective drugs for hypercholesteloremia. However, a significant side effect of statin treatment is rhabdomyolysis. In order to study the effect of statins in skeletal muscle cells, we used a DNA microarray analysis to investigate the changes in gene expression profiles brought about by statins in two skeletal muscle cell lines, namely, differentiated rat L6 myotubes and a human skeletal muscle cell line (hSkMC). In both cell lines, the statins (atorvastatin, cerivastatin and pitavastatin) induced the expression of four genes, which relate to cholesterol metabolism, namely, HMG-CoA synthase 1, HMG-CoA reductase, farnesyl diphosphate synthase and isopentenyl-diphosphate delta isomerase. Statin inhibited the synthesis of cholesterol at least five times more effectively in hSkMCs than in the hepatocytes. In addition, unlike in osteoblasts or coronary artery smooth muscle cells, statins upregulated the mRNA expression of cholesterol-associated enzymes in hSkMCs. These results provide basic information on skeletal muscle cells treated with statins and indicate that the cells are sensitive to the inhibition of HMG-CoA reductase, which may be related to the pathogenesis of muscle damage in statin therapy.
Morikawa
Shigeru
S
Laboratory for Systems Biology and Medicine, RCAST, The University of Tokyo, Tokyo, Japan.
Murakami
Takeshi
T
Yamazaki
Hiroyuki
H
Izumi
Akashi
A
Saito
Yasushi
Y
Hamakubo
Takao
T
Kodama
Tatsuhiko
T
D000818:Animals; D000069059:Atorvastatin; D018929:Cell Culture Techniques; D002784:Cholesterol / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology; D032448:Myoblasts, Skeletal / Q000187:drug effects* / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D011804:Quinolines; D012333:RNA, Messenger; D002784:Cholesterol; D000069059:Atorvastatin; C086276:cerivastatin; C108475:pitavastatin