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  • Meeting abstract
  • Open Access

Activation of RhoB in simvastatin-induced apoptosis of differentiated human skeletal muscle cells

  • 1,
  • 2,
  • 3 and
  • 1Email author
BMC Pharmacology20077 (Suppl 2) :A16

  • Published:


  • Cholesterol
  • Protein Level
  • mRNA Level
  • Mitochondrial Membrane
  • Simvastatin

Statins are well-tolerated cholesterol lowering drugs. However, in rare cases myotoxicity or even rhabdomyolysis occur. We have recently shown that in vitro statins are able to induce apoptosis in differentiated human skeletal muscle cells. In particular, simvastatin triggers the mitochondrial pathway of apoptosis via translocation of Bax from the cytosol to the mitochondrial membrane. Accordingly, caspase 9 and caspase 3 were consecutively activated. Here we show that an early event in simvastatin action is up-regulation of RhoB on mRNA level which is paralleled by the downstream Krüppel-like factor-2 (KLF-2) and KLF-6. Moreover, the level of active, GTP-bound RhoB was increased in simvastatin-treated cells in a concentration-dependent manner as determined by Rhotekin pull-down assay. Up-regulation of RhoB on mRNA and protein level was dependent on HMG-CoA reductase inhibition. Interestingly, the up-regulation of RhoB was paralleled by caspase 2 activation, which might be directly associated with RhoB and therefore be required for the cytotoxic effect of simvastatin.



This work was supported by the GEN-AU Dragon Project to M.H.

Authors’ Affiliations

Institute of Pharmacology, Medical University of Vienna, Austria
Department of Anesthesiology and Critical Care Medicine, Medical University of Vienna, Austria
Institute of Toxicology, Medical School Hannover, Germany


© Zörgiebel et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.