期刊
AGING-US
卷 8, 期 12, 页码 3400-+出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101130
关键词
endometrial stem cells; senescence; autophagy; calcium; oxidative stress
资金
- Russian Science Foundation [14-50-00068]
- Federal Agency of Scientific Organizations (Russia)
- Russian Foundation for Basic Research [16-34-00081mol_a, 14-04-01720, 14-04-00227]
Intracellular calcium ([Ca2+](i)) has been reported to play an important role in autophagy, apoptosis and necrosis, however, a little is known about its impact in senescence. Here we investigated [Ca2+](i) contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal H2O2-treatment resulted in a rapid calcium release from intracellular stores mediated by the activation of PLC/IP3/IP3R pathway. Notably, further senescence development was accompanied by persistently elevated [Ca2+] i levels. In H2O2-treated hMESCs, [Ca2+](i) chelation by BAPTA-AM (BAPTA) was sufficient to prevent the expansion of the senescence phenotype, to decrease endogenous reactive oxygen species levels, to avoid G0/G1 cell cycle arrest, and finally to retain proliferation. Particularly, loading with BAPTA attenuated phosphorylation of the main DNA damage response members, including ATM, 53BP1 and H2A. X and reduced activation of the p53/p21/Rb pathway in H2O2-stimulated cells. Next, we revealed that BAPTA induced an early onset of AMPK-dependent autophagy in H2O2-treated cells as confirmed by both the phosphorylation status of AMPK/mTORC1 pathway and the dynamics of the LC3 lipidization. Summarizing the obtained data we can assume that calcium chelation is able to trigger short-term autophagy and to prevent the premature senescence of hMESCs under oxidative stress.
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