Ke. Fladmark et al., FAS APO-1(CD95)-INDUCED APOPTOSIS OF PRIMARY HEPATOCYTES IS INHIBITEDBY CAMP/, Biochemical and biophysical research communications, 232(1), 1997, pp. 20-25
Fas/APO-1(CD-95) activation induced rapid apoptotic cell death of prim
ary rat hepatocytes in suspension culture. Activators of cAMP-dependen
t protein kinase (glucagon and N-6-benzoyl-cAMP) protected against apo
ptosis, whereas the specific cAMP-kinase inhibitor (Rp)-8-Br-cAMPS enh
anced Pas-induced death. The latter observation indicated that even th
e basal cAMP level may provide partial protection against Pas-induced
hepatocyte apoptosis. Two-dimensional gel electrophoresis revealed dec
reased phosphorylation of several proteins in Pas-activated cells. Mos
t of these dephosphorylations were attenuated or not observed in cells
simultaneously stimulated by anti-Pas and cAMP, indicating a tight co
rrelation between the dephosphorylations and death. Elevation of cAMP
rescued the cells not only from the Pas-induced morphological changes
and dephosphorylation, but also from functional deterioration. Whereas
cells treated with anti-Pas alone quickly lost plating efficiency, he
patocytes co-treated with glucagon retained their ability to adhere an
d spread on a collagen substratum. (C) 1997 Academic Press.