Gw. Meisenholder et al., EVENTS IN APOPTOSIS - ACIDIFICATION IS DOWNSTREAM OF PROTEASE ACTIVATION AND BCL-2 PROTECTION, The Journal of biological chemistry, 271(27), 1996, pp. 16260-16262
Cytoplasmic acidification is now recognized as a feature of apoptosis
in a variety of systems, However, its relation to other events in the
process of apoptosis is not yet characterized, In this work, we examin
ed the effect of BCL-2 overexpression on acidification mediated by cyc
loheximide treatment or Fas Ligation in Jurkat T-lymphoblasts. We find
that BCL-2 overexpression attenuates cytoplasmic acidification and ap
optosis detected by annexin V labeling, Acidification and phosphatidyl
serine externalization were found to occur concurrently. We also exami
ned the requirement for protease activation for cytoplasmic acidificat
ion to occur and found that inhibition of interleukin-1 beta convertin
g enzyme/CED-3 family proteases (using carbobenzoxy-Val-Ala-Asp-fluoro
methylketone, an inhibitor of these proteases) prevents acidification
and apoptosis mediated by Fas ligation, These studies suggest that BCL
-2 acts at a point upstream of acidification and that protease activat
ion is also upstream of acidification.