Involvement of Sox-4 in the cytochrome c-dependent AIF-independent apoptotic pathway in HeLa cells induced by ？12-prostaglandin J2

• Published in: Experimental & molecular medicine 2004, 36(5), , pp.444-453
• Main Authors: 김보은, 이정화, 김호식, 권오주, 정성환, 김인경
• Format: Article
• Language: Korean
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

Δ12-Prostaglandin (PG) J2 is known to elicit an anti-neoplastic effects via apoptosis induction. Previous study showed Δ12-PGJ2-induced apoptosis utilized caspase cascade through cytochrome c-dependent pathways in HeLa cells. In this study, the cellular mechanism of Δ12-PGJ2- induced apoptosis in HeLa cells, specifically, the role of two m itochondrial factors; bcl-2 and apoptosis-inducing factor (AIF) was investigated. Bcl-2 attenuated Δ12-PGJ2-induced caspase activation, loss of mitochondrial transmembrane potential (Δψm), nuclear fragmentation, DNA laddering, and growth curve inhibition for approximately 24 h, but not for longer time. AIF was not released from mitochondria, even if the Δψm was dissipated. One of the earliest events observed in Δ12-PGJ2-induced apoptotic events was dissipation of Δψm, the process known to be inhibited by bcl-2. Pre-treatment of z-VADfmk, the pan-caspase inhibitor, resulted in the attenuation of Δψm depolarization in Δ12-PGJ2- induced apoptosis. Up-regulation of Sox-4 protein by Δ12-PGJ2 was observed in HeLa and bcl-2 overexpressing HeLa B4 cell lines. Bcl-2 overexpression did not attenuate the expression of Sox-4 and its expression coincided with other apoptotic events. These results suggest tha t Δ12-PGJ2 induced Sox-4 expression may activate another upstream caspases excluding the caspase 9-caspase 3 cascade of mitochondrial pathway. These and previous findings together suggest that Δ12-PGJ2-induced apoptosis in HeLa cells is caspase-dependent, AIF-independent events which may be affected by Sox-4 protein expression up-regulated by Δ12-PGJ2. KCI Citation Count: 8