Cellular defense against UVB-induced phototoxicity by cytosolic NADP(+)-dependent isocitrate dehydrogenase.
Ultraviolet (UV) radiation is known as a major cause of skin photoaging and photocarcinogenesis. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species. Recently, we have shown that NADP(+)-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study we investigated the role of cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc) against UV radiation-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to UVB (312 nm), the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly overexpressed IDPc exhibited enhanced resistance against UV radiation, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against UV radiation-induced oxidative injury.
Jo
Seung-Hee
SH
Department of Genetic Engineering, Kyungpook National University, Daegu, Korea.
Lee
So-Hyun
SH
Chun
Hang Suk
HS
Lee
Su Min
SM
Koh
Ho-Jin
HJ
Lee
Sung-Eun
SE
Chun
Jang-Soo
JS
Park
Jeen-Woo
JW
Huh
Tae-Lin
TL
D016475:3T3 Cells; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D019610:Cytoprotection; D003600:Cytosol / Q000201:enzymology; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000528:radiation effects; D051379:Mice; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D014466:Ultraviolet Rays
D000975:Antioxidants; D017382:Reactive Oxygen Species; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D005978:Glutathione