RRC ID 43225
Author Koike M, Ninomiya Y, Koike A.
Title Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cells.
Journal J Dermatol
Abstract The skin is an external organ that is most frequently exposed to radiation. It is important to elucidate the influence of radiation exposure on the skin at the molecular level. To identify radiation-responsive genes in human skin cells, we used microarray technology to examine the effects of irradiation on 641 genes in normal human epidermal keratinocytes at 4 h and 8 h postirradiation with a cytotoxic dose of X-ray (10 Gy). We found that 18 genes were upregulated and 35 genes were downregulated in keratinocytes at 4 h and/or 8 h postirradiation. Ninjurin, whose function remains unknown in keratinocytes, was induced most strongly by X-irradiation. Several known apoptosis-related genes, such as TSC22, were also upregulated. We characterized Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The induction of the expression of Ninjurin and TSC22 mRNA in keratinocytes following high-dose X-irradiation was confirmed by northern blot analysis. In dermal fibroblasts, Ninjurin, but not TSC22, was induced after X-ray irradiation. The dependence of both gene expression on the status of an apoptosis regulator, p53, was found. In addition, the expression of both mRNA was induced upon treatment with an apoptosis inducer, etoposide. On the other hand, TSC22, but not Ninjurin, was induced and accumulated in keratinocytes upon treatment with an apoptosis inducer, anisomycin. However, in transient expression assay, EYFP-TSC22, as well as EYFP-Ninjurin or EYFP alone, did not induce apoptosis in keratinocytes in contrast to EYFP-GADD45. Taken together, these findings have important implications on the understanding of the mechanism underlying the complex response of skin cells following X-irradiation.
Volume 35(1)
Pages 6-17
Published 2008-1-1
DOI 10.1111/j.1346-8138.2007.00403.x
PMID 18181769
MeSH Anisomycin / pharmacology Apoptosis / genetics Apoptosis / physiology Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism Apoptosis Regulatory Proteins / physiology Blotting, Northern Cell Adhesion Molecules, Neuronal / genetics Cell Adhesion Molecules, Neuronal / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line Dose-Response Relationship, Radiation Etoposide / pharmacology Gene Expression Profiling Gene Expression Regulation / genetics Gene Expression Regulation / physiology Gene Expression Regulation / radiation effects* Humans Keratinocytes / drug effects Keratinocytes / metabolism Keratinocytes / physiology Keratinocytes / radiation effects* Nerve Growth Factors / genetics Nerve Growth Factors / metabolism* Oligonucleotide Array Sequence Analysis Plasmids RNA, Messenger / analysis Repressor Proteins / genetics Repressor Proteins / metabolism* Repressor Proteins / physiology Transfection
IF 3.072
Times Cited 9
Human and Animal Cells VA-13(RCB0251)