Details

Autor(en) / Beteiligte

• Borodkina, Aleksandra V
• Shatrova, Alla N
• Deryabin, Pavel I
• Griukova, Anastasiia A
• Abushik, Polina A
• Antonov, Sergei M
• Nikolsky, Nikolay N
• Burova, Elena B

Titel

Calcium alterations signal either to senescence or to autophagy induction in stem cells upon oxidative stress

Ist Teil von

• Aging (Albany, NY.), 2016-12, Vol.8 (12), p.3400-3418

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Intracellular calcium ([Ca ] ) 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 [Ca ] contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal H O -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 [Ca ] levels. In H O -treated hMESCs, [Ca ] 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 H O -stimulated cells. Next, we revealed that BAPTA induced an early onset of AMPK-dependent autophagy in H O -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.