Specific Expression of Bax-ω in Pancreatic β-Cells Is Down-Regulated by Cytokines before the Onset of Apoptosis.

Cytokines have been implicated in the process of pancreatic -cell destruction that leads to type 1 diabetes. This study investigates the -cell expression of proand antiapoptotic proteins from the Bcl-2 family and their variation during cytokine-mediated apoptosis. Exposure of rat -cells to the combination of IL-1 plus interferoncauses a time-dependent increase in apoptotic cells starting after 3 d (<10% on d 3 and 28 2% on d 7). This effect was preceded by a marked downregulation of two antiapoptotic proteins, Bcl-2 and Bax(respectively reduced by 60% and 80% after 3 d), whereas no changes occurred in the expression of Bcl-xL and the proapoptotic protein Bax. No apoptosis or down-regulation of Bcl-2 and Baxproteins was observed with individual cytokines or in the presence of N-methyl-L-arginine, an inhibitor of nitric oxide synthase. The lowered Bcl-2 protein content was associated with a decrease in Bcl-2 mRNA, which was initiated after 24 h of exposure. In MIN6 cells, the cytokine-induced suppression of Bcl-2and Bax, and apoptosis, occurred within 24 h. Primary rat -cells exhibited a higher expression of Baxthan MIN6 cells or than other rat cell types. These data suggest that suppression of the antiapoptotic proteins Bcl-2 and Baxmediates cytokine-induced apoptosis of -cells. The -cell-specific expression of Baxmakes this protein a possible effector in the protection of this cell type against apoptosis. (Endocrinology 143: 320–326, 2002)