Role of protein kinase C delta in X-ray-induced apoptosis of keratinocyte
Young-Sook Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorKyung-Cheol Sohn
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorKi-Hwan Kim
Department of Radiation Oncology, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorMoon-June Cho
Department of Radiation Oncology, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorGang Min Hur
Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorTae-Jin Yoon
Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju, Korea
Search for more papers by this authorSung Kyu Kim
Department of Therapeutic Radiology and Oncology, College of Medicine, Yeungnam University, Daegu, Korea
Search for more papers by this authorKyungmoon Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorJeung-Hoon Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorChang Deok Kim
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorYoung-Sook Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorKyung-Cheol Sohn
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorKi-Hwan Kim
Department of Radiation Oncology, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorMoon-June Cho
Department of Radiation Oncology, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorGang Min Hur
Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorTae-Jin Yoon
Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju, Korea
Search for more papers by this authorSung Kyu Kim
Department of Therapeutic Radiology and Oncology, College of Medicine, Yeungnam University, Daegu, Korea
Search for more papers by this authorKyungmoon Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorJeung-Hoon Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorChang Deok Kim
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorAbstract
Abstract: In this study, we investigated the process of X-ray-induced apoptosis of skin keratinocyte, and the functional role of protein kinase C delta (PKCδ) and downstream signalling cascade. High-dose X-ray irradiation (10 Gy) led to the apoptosis of HaCaT keratinocyte, accompanied by PKCδ cleavage. Treatment with PKCδ inhibitor and adenoviral transduction of dominant-negative PKCδ 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 PKCδ markedly blocked the X-ray-induced phosphorylation of ERK1/2, suggesting that ERK1/2 is the functional downstream effector of PKCδ. Next, we investigated the difference between UVB and X-ray response. UVB induced the apoptosis of keratinocyte in a PKCδ-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 PKCδ 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.
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