Fas-mediated apoptosis in a rat acinar cell line is dependent on caspase-1 activity.
Apoptosis plays an important role in the dysfunction of exocrine glands. Fas is a death-inducing receptor found on many types of cells including epithelial acinar cells. To elucidate the intracellular mechanism of Fas-mediated cell death in exocrine glands, an epithelial acinar cell line, SMG-C6, was studied. Caspase-1, -3, -8, and -9 activities were elevated in SMG-C6 cells after the induction of apoptosis by soluble Fas ligand (FasL). The activation of caspase-1 and -8 occurred prior to caspase-3 and -9 activation. The caspase-1 inhibitor, zYVAD-fmk, was effective in preventing cell death, whereas the caspase-3 and -8 inhibitors (ac-DEVD-CHO and ac-IETD-CHO, respectively) were not. zYVAD-fmk was able to inhibit caspase-3 activation indicating 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 study shows that caspase-1 participates in Fas-mediated apoptosis of epithelial cells by initiating the caspase cascade.
Aiba-Masago
S
S
Division of Clinical Immunology, Department of Medicine, Mail Code 7874, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Masago
R
R
Vela-Roch
N
N
Talal
N
N
Dang
H
H
D000818:Animals; D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D053222:Fas Ligand Protein; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008954:Models, Biological; D051381:Rats; D012469:Salivary Glands / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000201:enzymology / Q000473:pathology*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1