Fas-mediated apoptosis in a rat acinar cell line is dependent on caspase-1activity

Apoptosis plays an important role in the dysfunction of exocrine glands. Fa s is a death-inducing receptor found on many types of cells including epith elial acinar cells. To elucidate the intracellular mechanism of Fas-mediate d cell death in exocrine glands, an epithelial acinar cell line, SMG-C6, wa s studied. Caspase-1, -3, -8, and -9 activities were elevated in SMG-C6 cel ls after the induction of apoptosis by soluble Fas ligand (FasL). The activ ation of caspase-1 and -8 occurred prior to caspase-3 and -9 activation. Th e caspase-1 inhibitor, zYVAD-fmk, was effective in preventing cell death, w hereas the caspase-3 and -8 inhibitors (ac-DEVD-CHO and ac-IETD-CHO, respec tively) were not. zYVAD-fmk was able to inhibit caspase-3 activation indica ting that caspase-1 is upstream to caspase-3. Furthermore, kinetic studies show that caspase-1 is an early event in the Fas apoptotic pathway. This st udy shows that caspase-1 participates in Fas-mediated apoptosis of epitheli al cells by initiating the caspase cascade. (C) 2001 Elsevier Science Inc. All rights reserved.