Caspase activation and disruption of mitochondrial membrane potential during UV radiation-induced apoptosis of human keratinocytes requires activation of protein kinase C.
The induction of apoptosis in human keratinocytes by UV radiation involves caspase-mediated cleavage and activation of protein kinase C delta (PKCdelta). Here we examined the role of PKC activation in caspase activation and disruption of mitochondria function by UV radiation. Inhibition of PKC partially blocked UV radiation-induced cleavage of PKCdelta, pro-caspase-3, and pro-caspase-8, and the activation of these caspases. PKC inhibition also blocked the UV-induced loss of mitochondria membrane potential, but did not block the release of cytochrome c from mitochondria. Expression of the active catalytic domain of PKCdelta was sufficient to induce apoptosis and disrupt mitochondrial membrane potential, however a kinase inactive PKCdelta catalytic domain did not. Furthermore, the PKCdelta catalytic fragment generated following UV radiation localized to the mitochondria fraction, as did ectopically expressed PKCdelta catalytic domain. These results identify a functional role for PKC activation in potentiating caspase activation and disrupting mitochondrial function during UV-induced apoptosis.
Denning
M F
MF
Department of Pathology, Cardinal Bernardin Cancer Center, Skin Cancer Research Program, Loyola University Medical Center, Maywood, IL 60153, USA. mdennin@lumc.edu
Wang
Y
Y
Tibudan
S
S
Alkan
S
S
Nickoloff
B J
BJ
Qin
J-Z
JZ
D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008564:Membrane Potentials / Q000528:radiation effects; D008928:Mitochondria / Q000502:physiology / Q000528:radiation effects*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D014466:Ultraviolet Rays
D007527:Isoenzymes; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D020169:Caspases