PMID- 32679123
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20211204
IS  - 1872-6216 (Electronic)
IS  - 0047-6374 (Linking)
VI  - 190
DP  - 2020 Sep
TI  - Nifedipine-induced AMPK activation alleviates senescence by increasing autophagy 
      and suppressing of Ca(2+) levels in vascular smooth muscle cells.
PG  - 111314
LID - S0047-6374(20)30110-X [pii]
LID - 10.1016/j.mad.2020.111314 [doi]
AB  - Calcium (Ca(2+)) homeostasis is disrupted during aging in several cell types and 
      this disruption leads to autophagy impairment. The mechanisms regarding Ca(2+), 
      senescence, and autophagy need to be elucidated. Therefore, we hypothesized that 
      cellular senescence can be improved by regulating Ca(2+) level and autophagy 
      activity. We identified that hydrogen peroxide (H(2)O(2))-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 H(2)O(2)-induced senescence by reducing 
      Ca(2+) entry, autophagy impairment and mTOR signaling, and this suppression was 
      found to be related to senescence-associated beta-galactosidase (SA-beta-gal) activity 
      and the expressions of senescence marker protein 30 (SMP30), p53, and p21. 
      Furthermore, H(2)O(2)-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 Ca(2+) levels.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Kim, Seul Gi
AU  - Kim SG
AD  - Department of Pharmacology, College of Medicine, Yeungnam University, 170 
      Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea; Smart-aging Convergence 
      Research Center, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, 
      Nam-Gu, Daegu 42415, Republic of Korea.
FAU - Sung, Jin Young
AU  - Sung JY
AD  - Department of Pharmacology, College of Medicine, Yeungnam University, 170 
      Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea; Smart-aging Convergence 
      Research Center, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, 
      Nam-Gu, Daegu 42415, Republic of Korea.
FAU - Kim, Jae-Ryong
AU  - Kim JR
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam 
      University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea; Smart-aging 
      Convergence Research Center, College of Medicine, Yeungnam University, 170 
      Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea.
FAU - Choi, Hyoung Chul
AU  - Choi HC
AD  - Department of Pharmacology, College of Medicine, Yeungnam University, 170 
      Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea; Smart-aging Convergence 
      Research Center, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, 
      Nam-Gu, Daegu 42415, Republic of Korea. Electronic address: hcchoi@med.yu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200715
PL  - Ireland
TA  - Mech Ageing Dev
JT  - Mechanisms of ageing and development
JID - 0347227
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium-Binding Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.1.1.- (Carboxylic Ester Hydrolases)
RN  - EC 3.1.1.- (Rgn protein, rat)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - *Autophagy/drug effects/physiology
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - *Calcium Signaling/drug effects/physiology
MH  - Calcium-Binding Proteins/metabolism
MH  - Carboxylic Ester Hydrolases/metabolism
MH  - Cells, Cultured
MH  - *Cellular Senescence/drug effects/physiology
MH  - Muscle, Smooth, Vascular
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - Nifedipine/*pharmacology
MH  - Phosphorylation
MH  - Rats
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - AMPK
OT  - Autophagy
OT  - Ca(2+)
OT  - Nifedipine
OT  - Senescence
OT  - Vascular smooth muscle cell
EDAT- 2020/07/18 06:00
MHDA- 2021/09/14 06:00
CRDT- 2020/07/18 06:00
PHST- 2020/04/24 00:00 [received]
PHST- 2020/06/29 00:00 [revised]
PHST- 2020/07/10 00:00 [accepted]
PHST- 2020/07/18 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2020/07/18 06:00 [entrez]
AID - S0047-6374(20)30110-X [pii]
AID - 10.1016/j.mad.2020.111314 [doi]
PST - ppublish
SO  - Mech Ageing Dev. 2020 Sep;190:111314. doi: 10.1016/j.mad.2020.111314. Epub 2020 
      Jul 15.