PMID- 28797827
OWN - NLM
STAT- MEDLINE
DCOM- 20190517
LR  - 20211204
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 109
DP  - 2018 Aug
TI  - Interaction between mTOR pathway inhibition and autophagy induction attenuates 
      adriamycin-induced vascular smooth muscle cell senescence through decreased 
      expressions of p53/p21/p16.
PG  - 51-58
LID - S0531-5565(16)30443-0 [pii]
LID - 10.1016/j.exger.2017.08.001 [doi]
AB  - Cellular senescence is related to aging and extremely stable proliferative arrest 
      with active metabolism. Senescent cells can activate mammalian target of 
      rapamycin (mTOR) pathway, which plays a crucial role in the regulation of cell 
      metabolism, cellular growth, and autophagy in senescence-associated 
      cardiovascular diseases. Therefore, we examined whether mTOR pathway could induce 
      cellular senescence by inhibition of autophagy in vascular smooth muscle cells 
      (VSMCs). We found that adriamycin-induced VSMC senescence is accompanied by 
      increased activity of mTOR, a major controller of cell growth and a negative 
      regulator of autophagy. VSMC senescence induced by activation of mTOR pathway led 
      to reduced levels of signal-associated autophagy proteins, and inhibition of mTOR 
      pathway resulted in a drastic decrease in the number of senescence-associated 
      beta-galactosidase (SA-beta-gal)-stained cells and increased levels of 
      signal-associated autophagy proteins. Autophagic inhibition potentiated 
      adriamycin-induced mTOR pathway activation as well as increase in the number of 
      SA-beta-gal-stained VSMCs. Results of further experiments showed that mTOR pathway 
      inhibition regulates adriamycin-induced expression of senescence markers 
      (p53/p21/p16), which plays an important role in different aspects of cellular 
      aging. Taken together, these results support the idea that intervention to 
      modulate the interaction between mTOR pathway and autophagy could be a potential 
      strategy for longevity.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
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 - Lee, Kyung Young
AU  - Lee KY
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 - 20170807
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Cellular Senescence/*drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p16/*analysis
MH  - Cyclin-Dependent Kinase Inhibitor p21/*analysis
MH  - Doxorubicin/*toxicity
MH  - Muscle, Smooth, Vascular/cytology/*drug effects
MH  - Myocytes, Smooth Muscle/*drug effects/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/physiology
MH  - Tumor Suppressor Protein p53/*analysis
OTO - NOTNLM
OT  - Autophagy
OT  - VSMC senescence
OT  - mTOR
OT  - p16
OT  - p21
OT  - p53
EDAT- 2017/08/12 06:00
MHDA- 2019/05/18 06:00
CRDT- 2017/08/12 06:00
PHST- 2016/10/19 00:00 [received]
PHST- 2017/08/01 00:00 [revised]
PHST- 2017/08/01 00:00 [accepted]
PHST- 2017/08/12 06:00 [pubmed]
PHST- 2019/05/18 06:00 [medline]
PHST- 2017/08/12 06:00 [entrez]
AID - S0531-5565(16)30443-0 [pii]
AID - 10.1016/j.exger.2017.08.001 [doi]
PST - ppublish
SO  - Exp Gerontol. 2018 Aug;109:51-58. doi: 10.1016/j.exger.2017.08.001. Epub 2017 Aug 
      7.