Gadd45b deficiency promotes premature senescence and skin aging
Autor: | Priyanka Madireddi, Silvia Maifrede, Andrew Magimaidas, Dan A. Liebermann, Barbara Hoffman, Kaushiki Mukherjee |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Senescence senescence Cell cycle checkpoint Ultraviolet Rays DNA damage Biology medicine.disease_cause 03 medical and health sciences Research Paper: Gerotarget (Focus on Aging) medicine Animals Cells Cultured Cellular Senescence Cell Proliferation Mice Knockout Gerotarget Gadd45 Wild type Hydrogen Peroxide Fibroblasts Cell cycle Embryo Mammalian Oxidants Antigens Differentiation Skin Aging Cell biology G2 Phase Cell Cycle Checkpoints Oxygen Oxidative Stress 030104 developmental biology Oncology cell cycle arrest embryonic structures Immunology GADD45B Gadd45b Oxidative stress |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | The GADD45 family of proteins functions as stress sensors in response to various physiological and environmental stressors. Here we show that primary mouse embryo fibroblasts (MEFs) from Gadd45b null mice proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. The impaired proliferation and increased senescence in Gadd45b null MEFs is partially reversed by culturing at physiological oxygen levels, indicating that Gadd45b deficiency leads to decreased ability to cope with oxidative stress. Interestingly, Gadd45b null MEFs arrest at the G2/M phase of cell cycle, in contrast to other senescent MEFs, which arrest at G1. FACS analysis of phospho-histone H3 staining showed that Gadd45b null MEFs are arrested in G2 phase rather than M phase. H2O2 and UV irradiation, known to increase oxidative stress, also triggered increased senescence in Gadd45b null MEFs compared to wild type MEFs. In vivo evidence for increased senescence in Gadd45b null mice includes the observation that embryos from Gadd45b null mice exhibit increased senescence staining compared to wild type embryos. Furthermore, it is shown that Gadd45b deficiency promotes senescence and aging phenotypes in mouse skin. Together, these results highlight a novel role for Gadd45b in stress-induced senescence and in tissue aging. |
Databáze: | OpenAIRE |
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