Role of protein kinase Cdelta in UV-B-induced apoptosis of macrophages in vitro.
We have previously reported that murine peritoneal macrophages exposed to ultraviolet B (UV-B; 100 mJ/cm2) undergo apoptosis, as indicated by alterations in cell morphology, caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage, DNA fragmentation, sustained activation of p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) and inactivation of p42/44 MAPKs. It is now reported that macrophages undergoing UV-B-induced apoptosis show enhanced expression of protein kinase Cdelta (PKCdelta) in a time-dependent manner. Pretreatment of macrophages with PKCdelta-specific inhibitor rottlerin prior to the UV-B irradiation inhibits activation of caspase-3, PARP cleavage, DNA fragmentation and release of intracellular Ca2+. Inhibition of PKCdelta also blocks the sustained activation of p38 and JNK MAPKs as well as inactivation of p42/44 MAPKs. PKCalpha and PKCbeta1 expression also increases during UV-B-induced apoptosis in macrophages. Inhibition of these two isoforms with Go6976 slightly suppresses caspase-3 activation, PARP cleavage, DNA fragmentation and release of intracellular Ca2+, but has no effect on the sustained activation of p38/JNK MAPKs or inactivation of p42/44 MAPKs. It is, therefore, suggested that activation of PKCdelta might play an important role in the UV-B-induced apoptosis and that specific activated isoforms of PKC may have distinct functions in cell death.
Sodhi
Ajit
A
School of Biotechnology, Banaras Hindu University, Faculty of Science, Varanasi-221005, India. ajit.sodhi@lycos.com
Sethi
Gautam
G
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000528:radiation effects; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D061945:Caspase Inhibitors; D007527:Isoenzymes; D011065:Poly(ADP-ribose) Polymerases; C497259:Prkcd protein, mouse; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D018844:Cyclin-Dependent Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D002118:Calcium; D000095043:Cyclin-Dependent Kinase-Activating Kinase