title: Impaired PI3K/Akt signaling as a potential cause of failure to precondition rat hearts under conditions of simulated hyperglycemia.
abstract: The aim of the study was to evaluate the impact of simulated acute hyperglycemia (HG) on PI3K/Akt signaling in preconditioned and non-preconditioned isolated rat hearts perfused with Krebs-Henseleit solution containing normal (11 mmol/l) or elevated (22 mmol/l) glucose subjected to ischemia-reperfusion. Ischemic preconditioning (IP) was induced by two 5-min cycles of coronary occlusion followed by 5-min reperfusion. Protein levels of Akt, phosphorylated (activated) Akt (P-Akt), as well as contents of BAX protein were assayed (Western blotting) in cytosolic fraction of myocardial tissue samples taken prior to and after 30-min global ischemia and 40-min reperfusion. In "normoglycemic" conditions (NG), IP significantly increased P-Akt at the end of long-term ischemia, while reperfusion led to its decrease together with the decline of BAX levels as compared to non-preconditioned hearts. On the contrary, under HG conditions, P-Akt tended to decline in IP-hearts after long-term ischemia, and it was significantly higher after reperfusion than in non-preconditioned controls. No significant influence of IP on BAX levels at the end of I/R was observed under HG conditions. It seems that high glucose may influence IP-induced activation of Akt and its downstream targets, as well as maintain persistent Akt activity that may be detrimental for the heart under above conditions.
authors: Institute for Heart Research, Slovak Academy of Science, Bratislava, Slovak Republic. mzmzalesak@gmail.com.
authors: M
authors: M
authors: Zálešák
authors: P
authors: P
authors: Blažíček
authors: I
authors: I
authors: Gablovský
authors: V
authors: V
authors: Ledvényiová
authors: M
authors: M
authors: Barteková
authors: A
authors: A
authors: Ziegelhöffer
authors: T
authors: T
authors: Ravingerová
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism* / Q000628:therapy*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D017211:Treatment Failure
chemical_list: D001786:Blood Glucose; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt