期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 190, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2020.111314
关键词
Nifedipine; Ca2+; Autophagy; Senescence; AMPK; Vascular smooth muscle cell
资金
- Medical Research Center Program [2015R1A5A2009124]
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning
Calcium (Ca2+) homeostasis is disrupted during aging in several cell types and this disruption leads to autophagy impairment. The mechanisms regarding Ca2+, senescence, and autophagy need to be elucidated. Therefore, we hypothesized that cellular senescence can be improved by regulating Ca2+ level and autophagy activity. We identified that hydrogen peroxide (H2O2)-induced senescence was accompanied by Ca(2+ )elevation, impairment of autophagic flux and increase of mammalian target of rapamycin (mTOR) phosphorylation in VSMCs. The treatment of nifedipine dose-dependently suppressed H2O2-induced senescence by reducing Ca2+ entry, autophagy impairment and mTOR signaling, and this suppression was found to be related to senescence-associated 5-galactosidase (SA-beta-gal) activity and the expressions of senescence marker protein 30 (SMP30), p53, and p21. Furthermore, H2O2-induced autophagy impairment also accelerated senescence and accumulations of ubiquitinated proteins. AMPK inhibition or transfection with AMPK siRNA showed that the anti-senescence effect of nifedipine involved AMPK activation. These results suggest nifedipine-inducted AMPK activation suppresses VSMC senescence by regulating autophagic flux and Ca2+ levels.
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