Role of hsp105 in protection against stress-induced apoptosis in neuronal PC12 cells.
hsp105alpha is a stress protein characteristically highly expressed in the brain compared with other tissues in mammals. Here, to examine whether hsp105alpha plays a pivotal role in the nervous system, we tested the capability of hsp105alpha to protect against apoptosis in rat neuronal PC12 cells. Various stress treatments such as serum deprivation, heat shock, hydrogen peroxide, etoposide, and actinomycin D induced apoptosis in PC12 cells with characteristic shrinking of nuclei and chromatin. However, PC12 cells that constitutively overexpressed mouse hsp105alpha exhibited a strong protective effect against apoptosis induced by these stress treatments. Cleavage of poly(ADP-ribose) polymerase induced in PC12 cells by these treatments was inhibited in the constitutively overexpressed hsp105alpha cells. Furthermore, c-Jun N-terminal kinase (JNK) was activated in the cells treated with heat shock but not other treatments, and the heat-induced JNK activation was inhibited by the constitutive expression of hsp105alpha.Thus, hsp105alpha prevents not only heat-induced apoptosis by inhibiting JNK activation, but also prevents the apoptosis induced by other stressors through different pathways, and may play important roles in neuronal protection.
Hatayama
T
T
Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan. hatayama@mb.kyoto-phu.ac.jp
Yamagishi
N
N
Minobe
E
E
Sakai
K
K
D000818:Animals; D017209:Apoptosis; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology*; D006358:Hot Temperature; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020011:Protective Agents / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D014162:Transfection
D016895:Culture Media, Serum-Free; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C490783:Hsp105 protein, mouse; D020011:Protective Agents; D011506:Proteins; C499321:Parp1 protein, mouse; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases