PMID- 27619662
OWN - NLM
STAT- MEDLINE
DCOM- 20170206
LR  - 20220331
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 422
IP  - 1-2
DP  - 2016 Nov
TI  - The PI3K/Akt/mTOR pathway regulates the replicative senescence of human VSMCs.
PG  - 1-10
AB  - Replicative senescence of vascular smooth muscle cells (VSMCs) contributes to 
      aging as well as age-related cardiovascular diseases. Rapamycin can delay the 
      onset of aging-related diseases via inhibition of the mammalian target of 
      rapamycin (mTOR), but its role in vascular aging remains elusive. This study 
      investigated the involvement of mTOR signaling in replicative senescence of 
      VSMCs. Replicative senescence was induced by the extended passages of human 
      VSMCs. Aging-related cell morphology was observed. The aging-related proteins and 
      enzyme activity, and oxidative stress were measured. Significant increase in 
      SA-beta-gal activity and protein expression, p53 and p16 protein expression, 
      proliferation index (PI), malondialdehyde (MDA) concentration, superoxide 
      dismutase (SOD) and glutathione peroxidase (GPX) activity, and significant 
      decrease in telomerase activity was observed in aging VSMCs compared to young 
      cells. Significant activation of PI3K/Akt/mTOR signaling was observed in aging 
      cells but not young cells. Pretreatment of VSMCs with PI3K inhibitor blocked 
      while PI3K activator increased the changes of the above replicative 
      senescence-related parameters in VSMCs. Rapamycin and silencing of mTOR 
      expression inhibited replicative senescence in VSMCs through decreasing the level 
      of p-mTOR Ser(2448), p-mTOR Thr(2446), and S6K1 phosphorylation. This study for 
      the first time demonstrated that the PI3K/Akt/mTOR/S6K1 signal pathway plays an 
      important role in regulating replicative senescence of human VSMCs.
FAU - Tan, Pan
AU  - Tan P
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Wang, Yan-Jiao
AU  - Wang YJ
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Li, Shuang
AU  - Li S
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - He, Je-Yu
AU  - He JY
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Chen, Yi-Yin
AU  - Chen YY
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Deng, Hui-Qian
AU  - Deng HQ
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Huang, Wu
AU  - Huang W
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China.
FAU - Zhan, Jun-Kun
AU  - Zhan JK
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China. zhanjunkun@163.com.
FAU - Liu, You-Shuo
AU  - Liu YS
AD  - Geriatric Department of the Second Xiang-Ya Hospital, Institute of Aging and 
      Geriatric Research, Central South University, 139 Middle Renmin Road, Changsha, 
      410011, Hunan, People's Republic of China. liuyoushuo@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20160913
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cells, Cultured
MH  - Cellular Senescence/*physiology
MH  - Humans
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
OTO - NOTNLM
OT  - PI3K/Akt/mTOR
OT  - Replicative senescence
OT  - Vascular aging
OT  - Vascular smooth muscle cells
EDAT- 2016/09/14 06:00
MHDA- 2017/02/07 06:00
CRDT- 2016/09/14 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2016/08/06 00:00 [accepted]
PHST- 2016/09/14 06:00 [pubmed]
PHST- 2017/02/07 06:00 [medline]
PHST- 2016/09/14 06:00 [entrez]
AID - 10.1007/s11010-016-2796-9 [pii]
AID - 10.1007/s11010-016-2796-9 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2016 Nov;422(1-2):1-10. doi: 10.1007/s11010-016-2796-9. Epub 
      2016 Sep 13.