Hsp105 family proteins suppress staurosporine-induced apoptosis by inhibiting the translocation of Bax to mitochondria in HeLa cells.
Hsp105 (Hsp105alpha and Hsp105beta), major heat shock proteins in mammalian cells, belong to a subgroup of the HSP70 family, HSP105/110. Previously, we have shown that Hsp105alpha has completely different effects on stress-induced apoptosis depending on cell type. However, the molecular mechanisms by which Hsp105alpha regulates stress-induced apoptosis are not fully understood. Here, we established HeLa cells that overexpress either Hsp105alpha or Hsp105beta by removing doxycycline and examined how Hsp105 modifies staurosporine (STS)-induced apoptosis in HeLa cells. Apoptotic features such as the externalization of phosphatidylserine on the plasma membrane and nuclear morphological changes were induced by the treatment with STS, and the STS-induced apoptosis was suppressed by overexpression of Hsp105alpha or Hsp105beta. In addition, we found that overexpression of Hsp105alpha or Hsp105beta suppressed the activation of caspase-3 and caspase-9 by preventing the release of cytochrome c from mitochondria. Furthermore, the translocation of Bax to mitochondria, which results in the release of cytochrome c from the mitochondria, was also suppressed by the overexpression of Hsp105alpha or Hsp105beta. Thus, it is suggested that Hsp105 suppresses the stress-induced apoptosis at its initial step, the translocation of Bax to mitochondria in HeLa cells.
Yamagishi
Nobuyuki
N
Department of Biochemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Ishihara
Keiichi
K
Saito
Youhei
Y
Hatayama
Takumi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D050957:HSP110 Heat-Shock Proteins; C490783:Hsp105 protein, mouse; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D019311:Staurosporine