Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway

Akira Wagatsuma, Yuzo Takayama, Takayuki Hoshino, Masataka Shiozuka, Shigeru Yamada, Ryoichi Matsuda, Kunihiko Mabuchi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have shown that pharmacological inhibition of HSP90 ATPase activity induces apoptosis of myoblasts during their differentiation. However, the signaling pathways remain not fully characterized. We report that pharmacological targeting of HSP90 with 17-AAG activates the intrinsic pathway including caspase-dependent and caspase-independent pathways. 17-AAG induces the typical apoptotic phenotypes including PARP cleavage, chromatin condensation, and nuclear fragmentation with mitochondrial release of cytochrome c, Smac/DIABLO, procaspase-9 processing, and caspase-3 activation. AIF and EndoG redistribute from the mitochondria into the cytosol and are partially translocated to the nucleus in 17-AAG-treated cells. These results suggest that caspase-dependent and caspase-independent pathways should be considered in apoptosis of myogenic cells induced by inhibition of HSP90 ATPase activity.

Original languageEnglish
Pages (from-to)45-58
Number of pages14
JournalMolecular and cellular biochemistry
Volume445
Issue number1-2
DOIs
Publication statusPublished - Aug 1 2018

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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