title: Calcium alterations signal either to senescence or to autophagy induction in stem cells upon oxidative stress.
abstract: 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+]icontribution 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+]ilevels. In H2O2-treated hMESCs, [Ca2+]ichelation 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.
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
authors.forename: Aleksandra V
authors.initials: AV
authors.lastname: Borodkina
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
authors.forename: Alla N
authors.initials: AN
authors.lastname: Shatrova
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Deryabin
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
authors.forename: Anastasiia A
authors.initials: AA
authors.lastname: Griukova
authors.affiliation: Laboratory of Comparative Neurophysiology, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223, Russia.
authors.forename: Polina A
authors.initials: PA
authors.lastname: Abushik
authors.affiliation: Laboratory of Comparative Neurophysiology, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223, Russia.
authors.forename: Sergei M
authors.initials: SM
authors.lastname: Antonov
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
authors.forename: Nikolay N
authors.initials: NN
authors.lastname: Nikolsky
authors.affiliation: Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Burova
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D006861:Hydrogen Peroxide; D055372:AMP-Activated Protein Kinases; D002118:Calcium
keywords: autophagy; calcium; endometrial stem cells; oxidative stress; senescence