PMID- 20445122
OWN - NLM
STAT- MEDLINE
DCOM- 20101019
LR  - 20211203
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 51
IP  - 10
DP  - 2010 Oct
TI  - Altered mTOR signaling in senescent retinal pigment epithelium.
PG  - 5314-9
LID - 10.1167/iovs.10-5280 [doi]
AB  - PURPOSE: Mammalian target of rapamycin (mTOR)-mediated pathways play central 
      roles in regulating aging. The purpose of the present study was to characterize 
      the mTOR cascade in human retinal pigment epithelial (RPE) cells and to 
      investigate its potential roles in controlling RPE senescence. METHODS: 
      Expression of major components of the mTOR signaling networks was evaluated by 
      Western blot analyses. Formations of the two signaling complexes of mTOR, mTORC1, 
      and mTORC2 were determined by coimmunoprecipitation. The activation of mTORC1 was 
      monitored by measuring the phosphorylation status of the downstream substrate 
      protein S6. Senescence of the cultured human RPE cells was assessed by measuring 
      both the senescence associated-beta-galactosidase (SA-beta-Gal) activity and the 
      expression level of p16, a cyclin-dependent kinase inhibitor. RESULTS: Human RPE 
      cells contained functional mTORC1 and mTORC2 signaling complexes. The assembly 
      and activity of mTORC1 were regulated by upstream nutrient and growth factor 
      signals. The sensitivity of mTORC1 to extracellular nutrient stimuli increased in 
      RPE cells that had developed in vitro senescence. Suppression of the mTORC1 by 
      rapamycin prevented the appearance of senescence markers in the RPE. CONCLUSIONS: 
      The mTOR pathway presented age-associated changes in human RPE cells, and 
      downregulation of mTORC1 could delay the aging process of the RPE.
FAU - Chen, Yan
AU  - Chen Y
AD  - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, 
      Tennessee 37232, USA. yan.chen@vanderbilt.edu
FAU - Wang, Jian
AU  - Wang J
FAU - Cai, Jiyang
AU  - Cai J
FAU - Sternberg, Paul
AU  - Sternberg P
LA  - eng
GR  - R01 EY007892/EY/NEI NIH HHS/United States
GR  - K99 EY019706/EY/NEI NIH HHS/United States
GR  - EY08126/EY/NEI NIH HHS/United States
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - EY018715/EY/NEI NIH HHS/United States
GR  - R21 EY018715/EY/NEI NIH HHS/United States
GR  - EY07892/EY/NEI NIH HHS/United States
GR  - K99 EY019706-01A1/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100505
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (CRTC2 protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cellular Senescence/*physiology
MH  - Cyclin-Dependent Kinase Inhibitor p16/metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proteins
MH  - Retinal Pigment Epithelium/*cytology/metabolism
MH  - Ribosomal Protein S6/metabolism
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/metabolism
MH  - beta-Galactosidase/metabolism
PMC - PMC3066610
EDAT- 2010/05/07 06:00
MHDA- 2010/10/20 06:00
PMCR- 2011/04/01
CRDT- 2010/05/07 06:00
PHST- 2010/05/07 06:00 [entrez]
PHST- 2010/05/07 06:00 [pubmed]
PHST- 2010/10/20 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - iovs.10-5280 [pii]
AID - 10-5280 [pii]
AID - 10.1167/iovs.10-5280 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5314-9. doi: 10.1167/iovs.10-5280. 
      Epub 2010 May 5.