UV light induces premature senescence in Akt1-null mouse embryonic fibroblasts by increasing intracellular levels of ROS.
Akt/PKB plays a pivotal role in cell survival and proliferation. Previously, we reported that UV-irradiation induces extensive cell death in Akt2(-/-) mouse embryonic fibroblasts (MEFs) while Akt1(-/-) MEFs show cell cycle arrest. Here, we find that Akt1(-/-) MEFs exhibit phenotypic changes characteristics of senescence upon UV-irradiation. An enlarged and flattened morphology, a reduced cell proliferation and an increased senescence-associated beta-galactosidase (SA beta-gal) staining indicate that Akt1(-/-) MEFs undergo premature senescence after UV-irradiation. Restoring Akt1 expression in Akt1(-/-) MEFs suppressed SA beta-gal activity, indicating that UV-induced senescence is due to the absence of Akt1 function. Notably, levels of ROS were rapidly increased upon UV-irradiation and the ROS scavenger NAC inhibits UV-induced senescence of Akt1(-/-) MEFs, suggesting that UV light induces premature senescence in Akt1(-/-) MEFs by modulating intracellular levels of ROS. In conjunction with our previous work, this indicates that different isoforms of Akt have distinct function in response to UV-irradiation.
Jee
Hye Jin
HJ
Department of Biochemistry, Dong-A University, Busan, South Korea.
Kim
Hyun-Ju
HJ
Kim
Ae Jeong
AJ
Bae
Yoe-Sik
YS
Bae
Sun Sik
SS
Yun
Jeanho
J
D019588:Aging, Premature / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D017382:Reactive Oxygen Species; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt