Possible involvement of both mitochondria- and endoplasmic reticulum-dependent caspase pathways in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells

• Published in: Neuroscience letters Vol. 333; no. 1; pp. 25 - 28
• Main Authors: Kitamura, Yoshihisa, Inden, Masatoshi, Miyamura, Atsushi, Kakimura, Jun-ichi, Taniguchi, Takashi, Shimohama, Shun
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.11.2002; Elsevier
• Subjects: Ageing, cell death; Apoptosis - drug effects; Apoptosis - physiology; Bcl-2; Biological and medical sciences; Caspase Inhibitors; Caspases; Caspases - metabolism; Cell physiology; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - enzymology; Fundamental and applied biological sciences. Psychology; Human SH-SY5Y cells; Humans; Mitochondria - drug effects; Mitochondria - enzymology; Mitochondrial complex I; Molecular and cellular biology; Neuroblastoma - enzymology; Parkinson's disease; Rotenone; Rotenone - pharmacology; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - enzymology; Bcl-2; Parkinson's disease; Human SH-SY5Y cells; Mitochondrial complex I; Caspases; Endoplasmic reticulum; Rotenone; Human; Peptidases; Mitochondria; Cell line; Enzyme; Caspase; Hydrolases; Neuroblastoma; In vitro; Apoptosis
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(02)00964-3

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 2F 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.