Role of protein kinase C delta in X-ray-induced apoptosis of keratinocyte

• Published in: Experimental dermatology Vol. 18; no. 1; pp. 50 - 56
• Main Authors: Lee, Young-Sook, Sohn, Kyung-Cheol, Kim, Ki-Hwan, Cho, Moon-June, Hur, Gang Min, Yoon, Tae-Jin, Kim, Sung Kyu, Lee, Kyungmoon, Lee, Jeung-Hoon, Kim, Chang Deok
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2009; Blackwell
• Subjects: Apoptosis; Biological and medical sciences; Cell Cycle; Cell Line, Tumor; Dermatology; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Genes, Dominant; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Keratinocytes - enzymology; Keratinocytes - pathology; Keratinocytes - radiation effects; Medical sciences; mitogen-activated protein kinase; Phosphorylation; protein kinase C delta; Protein Kinase C-delta - physiology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Ultraviolet Rays; X-ray; X-Rays; Protein kinase C; Radiodiagnosis; Enzyme; Dermatology; Transferases; Mitogen-activated protein kinase; Exploration; protein kinase C delta; X ray; Radiography; Cell death; Keratinocyte; X-ray; Apoptosis
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2008.00761.x

:  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.