PMID- 26045804
OWN - NLM
STAT- MEDLINE
DCOM- 20160516
LR  - 20211203
IS  - 1936-2625 (Electronic)
IS  - 1936-2625 (Linking)
VI  - 8
IP  - 3
DP  - 2015
TI  - The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue 
      cellular respiration.
PG  - 2955-62
AB  - The purpose of this in vitro study was to develop a useful biomarker (e.g., 
      cellular respiration, or mitochondrial O2 consumption) for measuring activities 
      of mTOR inhibitors. It measured the effects of commonly used immunosuppressants 
      (sirolimus-rapamycin, tacrolimus, and cyclosporine) on cellular respiration in 
      target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target 
      of rapamycin (mTOR), a serine/ threonine kinase that supports nutrient-dependent 
      cell growth and survival, is known to control energy conversion processes within 
      the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known 
      as sirolimus or Rapamune(R)) have been shown to impair mitochondrial function. 
      Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin 
      (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent 
      lymphokine production leading to a reduced T-cell function. Sirolimus (10 muM) 
      inhibited renal (22%, P=0.002), hepatic (39%, P<0.001), and cardiac (42%, 
      P=0.005) cellular respiration. Tacrolimus and cyclosporine had no or minimum 
      effects on cellular respiration in these tissues. Thus, these results clearly 
      demonstrate that impaired cellular respiration (bioenergetics) is a sensitive 
      biomarker of the immunosuppressants that target mTOR.
FAU - Albawardi, Alia
AU  - Albawardi A
AD  - Department of Pathology, UAE University Al-Ain 17666, Abu Dhabi, United Arab 
      Emirates.
FAU - Almarzooqi, Saeeda
AU  - Almarzooqi S
AD  - Department of Pathology, UAE University Al-Ain 17666, Abu Dhabi, United Arab 
      Emirates.
FAU - Saraswathiamma, Dhanya
AU  - Saraswathiamma D
AD  - Department of Pathology, UAE University Al-Ain 17666, Abu Dhabi, United Arab 
      Emirates.
FAU - Abdul-Kader, Hidaya Mohammed
AU  - Abdul-Kader HM
AD  - Department of Medicine, UAE University Al-Ain 17666, Abu Dhabi, United Arab 
      Emirates.
FAU - Souid, Abdul-Kader
AU  - Souid AK
AD  - Department of Pediatrics, UAE University Al-Ain 17666, Abu Dhabi, United Arab 
      Emirates.
FAU - Alfazari, Ali S
AU  - Alfazari AS
AD  - Department of Medicine, UAE University Al-Ain 17666, Abu Dhabi, United Arab 
      Emirates.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20150301
PL  - United States
TA  - Int J Clin Exp Pathol
JT  - International journal of clinical and experimental pathology
JID - 101480565
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
RIN - Int J Clin Exp Pathol. 2015;8(10):13783. PMID: 26722609
MH  - Animals
MH  - Cell Respiration/*drug effects
MH  - Heart/drug effects
MH  - Immunosuppressive Agents/*pharmacology
MH  - Kidney/drug effects
MH  - Liver/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC4440113
OTO - NOTNLM
OT  - O2 consumption
OT  - cyclosporine
OT  - mTOR
OT  - oxidative phosphorylation
OT  - rapamycin
OT  - sirolimus
OT  - tacrolimus
EDAT- 2015/06/06 06:00
MHDA- 2016/05/18 06:00
PMCR- 2015/03/01
CRDT- 2015/06/06 06:00
PHST- 2014/11/23 00:00 [received]
PHST- 2015/03/02 00:00 [accepted]
PHST- 2015/06/06 06:00 [entrez]
PHST- 2015/06/06 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
PST - epublish
SO  - Int J Clin Exp Pathol. 2015 Mar 1;8(3):2955-62. eCollection 2015.