tailieunhanh - Báo cáo khoa học: Mammalian 105 kDa heat shock family proteins suppress hydrogen peroxide-induced apoptosis through a p38 MAPK-dependent mitochondrial pathway in HeLa cells

Hsp105aand Hsp105bare major heat shock proteins in mammalian cells that belong to a subgroup of the HSP70 family, HSP105⁄110. Previously, we have shown that Hsp105ahas opposite effects on stress-induced apop-tosis depending on the cell type. However, it is not fully understood how Hsp105 regulates stress-induced apoptosis. | ễFEBS Journal Mammalian 105 kDa heat shock family proteins suppress hydrogen peroxide-induced apoptosis through a p38 MAPK-dependent mitochondrial pathway in HeLa cells Nobuyuki Yamagishi Youhei Saito and Takumi Hatayama Department of Biochemistry Division of BiologicalSciences Kyoto PharmaceuticalUniversity Japan Keywords apoptosis H2O2 Hsp105 JNK p38 MAPK Correspondence T. Hatayama Department of Biochemistry Division of BiologicalSciences Kyoto PharmaceuticalUniversity 5 Nakauchi-cho Misasagi Yamashina-ku Kyoto 607-8414 Japan Fax 81 75 595 4758 Tel 81 75 595 4653 E-mail hatayama@ Received 28 April2008 revised 23 June 2008 accepted 15 July 2008 doi Hsp105a and Hsp105b are major heat shock proteins in mammalian cells that belong to a subgroup of the HSP70 family HSP105 110. Previously we have shown that Hsp105a 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 Hsp105a and Hsp105b regulate H2O2-induced apoptosis by using HeLa cells in which expression of Hsp105a or Hsp105b was regulated using doxycycline. Overexpression of Hsp105a and Hsp105b suppressed the activation of caspase-3 and caspase-9 by preventing the release of cytochrome c from mitochondria in H2O2-treated cells. Furthermore both c-Jun N-terminal kinase JNK and p38 mitogen-activated protein kinase p38 MAPK were activated by treatment with H2O2 and the activation of both kinases was suppressed by overexpression of Hsp105a and Hsp105p. However H2O2-induced apoptosis was suppressed by treatment with a potent inhibitor of p38 MAPK SB202190 but not a JNK inhibitor SP600125. These findings suggest that Hsp105a and Hsp105b suppress H2O2-induced apoptosis by suppression of p38 MAPK signaling one of the essential pathways for apoptosis. Heat shock proteins Hsps are a set of highly conserved proteins produced in response to .