TY - JOUR
T1 - Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway
AU - Wagatsuma, Akira
AU - Takayama, Yuzo
AU - Hoshino, Takayuki
AU - Shiozuka, Masataka
AU - Yamada, Shigeru
AU - Matsuda, Ryoichi
AU - Mabuchi, Kunihiko
N1 - Funding Information:
Acknowledgements This research was supported by MEXT (the Ministry of Education, Culture, Sports, Science and Technology) (Grant in Aid for Scientific Research (C), 25350882), Japan.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s11010-017-3250-3
DO - 10.1007/s11010-017-3250-3
M3 - Article
C2 - 29248972
AN - SCOPUS:85038093613
SN - 0300-8177
VL - 445
SP - 45
EP - 58
JO - Enzymologia
JF - Enzymologia
IS - 1-2
ER -