Role of protein kinase C delta in X-ray-induced apoptosis of keratinocyte.
In this study, we investigated the process of X-ray-induced apoptosis of skin keratinocyte, and the functional role of protein kinase C delta (PKCdelta) and downstream signalling cascade. High-dose X-ray irradiation (10 Gy) led to the apoptosis of HaCaT keratinocyte, accompanied by PKCdelta cleavage. Treatment with PKCdelta inhibitor and adenoviral transduction of dominant-negative PKCdelta clearly inhibited the X-ray-induced apoptosis of keratinocyte. In addition, X-ray induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and inhibition by ERK1/2 inhibitor abrogated the X-ray-induced apoptosis. Interestingly, overexpression of dominant-negative PKCdelta markedly blocked the X-ray-induced phosphorylation of ERK1/2, suggesting that ERK1/2 is the functional downstream effector of PKCdelta. Next, we investigated the difference between UVB and X-ray response. UVB induced the apoptosis of keratinocyte in a PKCdelta-dependent manner, similar to X-ray response. However, UVB irradiation induced the phosphorylation of c-jun N-terminal kinases (JNK) and inhibition of JNK significantly protected the UVB-induced apoptosis. These results demonstrate that PKCdelta is a key regulator in X-ray-induced apoptosis of keratinocyte and suggest that there is subtle difference in downstream signalling cascade between UVB and X-ray response of keratinocyte.
Lee
Young-Sook
YS
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Sohn
Kyung-Cheol
KC
Kim
Ki-Hwan
KH
Cho
Moon-June
MJ
Hur
Gang Min
GM
Yoon
Tae-Jin
TJ
Kim
Sung Kyu
SK
Lee
Kyungmoon
K
Lee
Jeung-Hoon
JH
Kim
Chang Deok
CD
D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology* / Q000528:radiation effects*; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014466:Ultraviolet Rays; D014965:X-Rays
D004791:Enzyme Inhibitors; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases