Cleavage of Bax is mediated by caspase‐dependent or ‐independent calpain activation in dopaminergic neuronal cells: protective role of Bcl‐2

• DOI: 10.1046/j.1471-4159.2001.00368.x
• Publication Date: 2003-03-12T06:55:21Z
• Authors: Won‐Seok Choi; Eun‐Hee Lee; Chul‐Woong Chung; Yong‐Keun Jung; Byung K. Jin; Seung U. Kim; Tae H. Oh; Takaomi C. Saido; Young J. Oh
• Keywords: Cysteine protease; Staurosporine

Two cysteine protease families, caspase and calpain, are known to participate in cell death. We investigated whether a stress‐specific activation pathway exists, what extent Bcl‐2 plays role preventing drug‐induced activity death dopaminergic neuronal line, MN9D. Staurosporine (STS) induced caspase‐dependent apoptosis while neurotoxin, MPP + largely caspase‐independent necrotic as determined by morphological biochemical criteria including cytochrome c release fluorogenic cleavage assay. At the late stage of both STS‐ ‐induced death, Bax was cleaved into an 18‐kDa fragment. This fragment appeared only mitochondria‐enriched heavy membrane fraction STS‐treated cells, whereas it detected exclusively cytosolic ‐treated cells. proteolytic be mediated calpain incubation with [ 35 S]methionine‐labelled Bax. Thus, cotreatment cells inhibitor blocked ‐ STS‐induced cleavage. Intriguingly, overexpression baculovirus‐derived inhibiting protein caspase, p35 or but not appears indicate that may either dependent independent within same However, rescued from In these paradigms prevented its associated our results suggest play protective primarily blocking