Abstract：
:Statins are the most common type of medicine used to treat hypercholesterolemia; however, they are associated with a low incidence of myotoxicity such as myopathy and rhabdomyolysis. The mechanisms for the adverse effects remain to be fully elucidated for safer chronic use and drug development. The results of our earlier work suggested that hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma A204 cells. In this study, we first confirmed the statin-induced autophagy by assessing other criteria, including induced expression of the autophagy-related genes, enhanced protein degradation of autophagy marker protein p62 and electron microscopic observation of induced formation of autophagosome. We next demonstrated that the extent of inhibition of HMG-CoA reductase in the cell is parallel with the ability of a statin to induce autophagy. Thus, the primary activity of statins causes autophagy in A204 cells. Considering the mechanism for the induction, we showed that statins induce autophagy by depleting cellular levels of geranylgeranyl diphosphate (GGPP) mostly through an unknown pathway that does not involve two major small G proteins, Rheb and Ras. Finally, we demonstrated that the ability of statins to induce autophagy parallels their toxicity to A204 cells and that both can be suppressed by GGPP.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Araki M,Maeda M,Motojima Kdoi
10.1016/j.ejphar.2011.10.044subject
Has Abstractpub_date
2012-01-15 00:00:00pages
95-103issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(11)01430-0journal_volume
674pub_type
杂志文章abstract：:Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalus membranaceus. This study is aimed to investigate AS-IV׳s effects on Ca(2+) channel activity of single cardiomyocytes and single Ca(2+) channels. Whole-cell Ca(2+) currents in freshly dissociated cardiomyocytes were measured using the whole-ce...
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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