Possible involvement of both mitochondria- and endoplasmic reticulum-dependent caspase pathways in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells.
Recently, it has been shown that rotenone, a specific inhibitor of mitochondrial complex I, is a useful tool in animal models of Parkinson's disease, but the mechanism of rotenone-induced neuronal death is not fully understood. In human neuroblastoma SH-SY5Y cells, rotenone induced the degradation of procaspases-12, -9 and -3, followed by cleavage of poly (adenosine diphosphate-ribose) polymerase, DNA fragmentation and cell death. Pretreatment with phorbol-12-myristate-13-acetate inhibited the rotenone-induced decrease in procaspases-9 and -3, but not that in procaspase-12. In contrast, benzyloxycarbonyl-Val-Ala-Asp(OCH(3))-CH(2)F inhibited the decrease in procaspase-12, but not those in procaspases-9 and -3 in this study. These results suggest that rotenone may induce activation of both mitochondria- and endoplasmic reticulum-dependent caspases in human SH-SY5Y cells.
Kitamura
Yoshihisa
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan. yo-kita@mb.kyoto-phu.ac.jp
Inden
Masatoshi
M
Miyamura
Atsushi
A
Kakimura
Jun-ichi
J
Taniguchi
Takashi
T
Shimohama
Shun
S
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009447:Neuroblastoma / Q000201:enzymology; D012402:Rotenone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D061945:Caspase Inhibitors; D012402:Rotenone; D020169:Caspases