279 521

Cited 34 times in

Inhibition of glycogen synthase kinase or the apoptotic protein p53 lowers the threshold of helium cardioprotection in vivo: the role of mitochondrial permeability transition

Authors
 Paul S. Pagel  ;  John G. Krolikowski  ;  Phillip F. Pratt Jr  ;  Yon Hee Shim  ;  Julien Amour  ;  David C. Warltier  ;  Dorothee Weihrauch 
Citation
 ANESTHESIA AND ANALGESIA, Vol.107(3) : 769-775, 2008 
Journal Title
ANESTHESIA AND ANALGESIA
ISSN
 0003-2999 
Issue Date
2008
MeSH
Animals ; Apoptosis* ; Atractyloside/pharmacology ; Benzothiazoles/metabolism ; Cardiotonic Agents/pharmacology* ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Glycogen Synthase Kinases/antagonists & inhibitors* ; Helium/chemistry ; Helium/pharmacology* ; Indoles/pharmacology ; Male ; Maleimides/pharmacology ; Mitochondria/metabolism ; Oxygen/metabolism ; Permeability* ; Rabbits ; Toluene/analogs & derivatives ; Toluene/metabolism ; Tumor Suppressor Protein p53/metabolism*
Keywords
Animals ; Apoptosis* ; Atractyloside/pharmacology ; Benzothiazoles/metabolism ; Cardiotonic Agents/pharmacology* ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Glycogen Synthase Kinases/antagonists & inhibitors* ; Helium/chemistry ; Helium/pharmacology* ; Indoles/pharmacology ; Male ; Maleimides/pharmacology ; Mitochondria/metabolism ; Oxygen/metabolism ; Permeability* ; Rabbits ; Toluene/analogs & derivatives ; Toluene/metabolism ; Tumor Suppressor Protein p53/metabolism*
Abstract
BACKGROUND: Prosurvival signaling kinases inhibit glycogen synthase kinase-3beta (GSK-3beta) activity and stimulate apoptotic protein p53 degradation. Helium produces cardioprotection by activating prosurvival kinases, but whether GSK and p53 inhibition mediate this process is unknown. We tested the hypothesis that inhibition of GSK or p53 lowers the threshold of helium cardioprotection via a mitochondrial permeability transition pore (mPTP)-dependent mechanism.

METHODS: Rabbits (n = 85) instrumented for hemodynamic measurement and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), or 1, 3, or 5 cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture (fraction of inspired oxygen concentration = 0.30) before LAD occlusion. Other rabbits received the GSK inhibitor SB 216763 (SB21; 0.2 or 0.6 mg/kg), the p53 inhibitor pifithrin-alpha (PIF; 1.5 or 3.0 mg/kg), or SB21 (0.2 mg/kg) or PIF (1.5 mg/kg) plus helium (1 cycle) before LAD occlusion in the presence or absence of the mPTP opener atractyloside (5 mg/kg).

RESULTS: Helium reduced (P < 0.05) myocardial infarct size (35 +/- 6 [n = 7], 25 +/- 4 [n = 7], and 20 +/- 3% [n = 6] of area at risk, 1, 3, and 5 cycles, respectively) compared with control (44 +/- 6% [n = 7]). SB21 (0.6 [n = 7] but not 0.2 mg/kg [n = 6]) and PIF (3.0 [n = 6] but not 1.5 mg/kg [n = 7]) also reduced necrosis. SB21 (0.2 mg/kg) or 1.5 mg/kg PIF (1.5 mg/kg) plus helium (1 cycle; n = 6 per group) decreased infarct size to an equivalent degree as three cycles of helium alone, and this cardioprotection was blocked by atractyloside (n = 7 per group).

CONCLUSIONS: Inhibition of GSK or p53 lowers the threshold of helium-induced preconditioning via a mPTP-dependent mechanism in vivo
Files in This Item:
T200805214.pdf Download
DOI
10.1213/ane.0b013e3181815b84
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Shim, Yon Hee(심연희) ORCID logo https://orcid.org/0000-0003-1921-3391
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108352
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links