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Mammalian 105 kDa heat shock family proteins suppress hydrogen peroxide‐induced apoptosis through a p38 MAPK‐dependent mitochondrial pathway in HeLa cells
Author(s) -
Yamagishi Nobuyuki,
Saito Youhei,
Hatayama Takumi
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06598.x
Subject(s) - p38 mitogen activated protein kinases , apoptosis , microbiology and biotechnology , hela , mapk/erk pathway , cytochrome c , kinase , hsp70 , heat shock protein , ask1 , protein kinase a , mitogen activated protein kinase , chemistry , mitochondrion , signal transduction , biology , mitogen activated protein kinase kinase , cell , biochemistry , gene
Hsp105α and Hsp105β are major heat shock proteins in mammalian cells that belong to a subgroup of the HSP70 family, HSP105/110. Previously, we have shown that Hsp105α has opposite effects on stress‐induced apoptosis depending on the cell type. However, it is not fully understood how Hsp105 regulates stress‐induced apoptosis. In this study, we examined how Hsp105α and Hsp105β regulate H 2 O 2 ‐induced apoptosis by using HeLa cells in which expression of Hsp105α or Hsp105β was regulated using doxycycline. Overexpression of Hsp105α and Hsp105β suppressed the activation of caspase‐3 and caspase‐9 by preventing the release of cytochrome c from mitochondria in H 2 O 2 ‐treated cells. Furthermore, both c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (p38 MAPK) were activated by treatment with H 2 O 2 , and the activation of both kinases was suppressed by overexpression of Hsp105α and Hsp105β. However, H 2 O 2 ‐induced apoptosis was suppressed by treatment with a potent inhibitor of p38 MAPK, SB202190, but not a JNK inhibitor, SP600125. These findings suggest that Hsp105α and Hsp105β suppress H 2 O 2 ‐induced apoptosis by suppression of p38 MAPK signaling, one of the essential pathways for apoptosis.