PMID- 30726893
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20211204
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 160
IP  - 4
DP  - 2019 Apr 1
TI  - Aldosterone Modulates the Mechanistic Target of Rapamycin Signaling in Male Mice.
PG  - 716-728
LID - 10.1210/en.2018-00989 [doi]
AB  - Both mechanistic target of rapamycin (mTOR) pathway and aldosterone are 
      implicated in the development of cardiovascular and renal disease. However, the 
      interaction between aldosterone and the mTOR pathway is unknown. We hypothesized 
      the following: that (i) increased aldosterone will modulate the activity of the 
      mTORC1 and mTORC2 molecular pathways in the heart and kidney; (ii) a physiologic 
      increase in aldosterone will affect these pathways differently than a 
      pathophysiologic one; and (iii) the changes in the mTOR level/activity will 
      differ between the heart and kidney. In both kidney and heart tissues, 
      phosphorylation of mTOR is significantly decreased when aldosterone levels are 
      physiologically increased (by dietary sodium restriction), followed by a decrease 
      in phosphorylated p70S6K1 in cardiac, but not renal, tissue. Sirtuin 1, an 
      epigenetic modulator, is decreased in the heart but increased in the kidney. 
      Conversely, pathophysiologic aldosterone levels (an infusion for 3 weeks) had 
      divergent effects on phosphorylated mTOR and the downstream substrates of mTORC1 
      and mTORC2 in cardiac and renal tissues. Increased aldosterone levels 
      significantly alter mTOR activity in the heart and kidney. In the kidney, 
      substantial differences were noted if the increase was produced physiologically 
      vs pathophysiologically, suggesting that mTOR activity, in part, may mediate 
      aldosterone-induced renal damage. Thus, modulating mTOR activity may reduce 
      aldosterone-dependent renal damage similar to mineralocorticoid receptor blockade 
      but potentially with less adverse side effects.
CI  - Copyright (c) 2019 Endocrine Society.
FAU - Brooks, Danielle L
AU  - Brooks DL
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
FAU - Garza, Amanda E
AU  - Garza AE
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
FAU - Katayama, Isis A
AU  - Katayama IA
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
FAU - Romero, Jose R
AU  - Romero JR
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
FAU - Adler, Gail K
AU  - Adler GK
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
FAU - Pojoga, Luminita H
AU  - Pojoga LH
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
FAU - Williams, Gordon H
AU  - Williams GH
AD  - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's 
      Hospital, Boston, Massachusetts.
LA  - eng
GR  - R56 HL114765/HL/NHLBI NIH HHS/United States
GR  - R01 HL096518/HL/NHLBI NIH HHS/United States
GR  - R01 HL144779/HL/NHLBI NIH HHS/United States
GR  - K24 HL103845/HL/NHLBI NIH HHS/United States
GR  - T32 HL007609/HL/NHLBI NIH HHS/United States
GR  - R01 HL104032/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 4964P6T9RB (Aldosterone)
RN  - 6995V82D0B (Eplerenone)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Aldosterone/*pharmacology
MH  - Animals
MH  - Eplerenone/pharmacology
MH  - Heart/*drug effects
MH  - Kidney/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Myocardium/metabolism
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6397424
EDAT- 2019/02/07 06:00
MHDA- 2019/12/18 06:00
PMCR- 2020/02/06
CRDT- 2019/02/07 06:00
PHST- 2018/11/20 00:00 [received]
PHST- 2019/01/31 00:00 [accepted]
PHST- 2019/02/07 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/02/07 06:00 [entrez]
PHST- 2020/02/06 00:00 [pmc-release]
AID - 5307699 [pii]
AID - endo_201800989 [pii]
AID - 10.1210/en.2018-00989 [doi]
PST - ppublish
SO  - Endocrinology. 2019 Apr 1;160(4):716-728. doi: 10.1210/en.2018-00989.