Hyperglycemia-Induced Oxidative Stress Abrogates Remifentanil Preconditioning-Mediated Cardioprotection in Diabetic Rats by Impairing Caveolin-3-Modulated PI3K/Akt and JAK2/STAT3 Signaling
N-Acetylcysteine- (NAC-) restored remifentanil protection against HG and H/R-induced injury involves caveolae-modulated Akt and STAT3 activation in isolated cardiomyocytes. Isolated rat cardiomyocytes were exposed to high glucose (HG, 25 mmol/L) with or without treatment of methyl-β-cyclodextrin (CD, 10 μM), wortmannin (Wort, 100 nM), AG490 (AG, 50 μM), or combination of remifentanil (Remi, 2.5 μM) and NAC (1 mmol/L) for 36 h, then subjected to 4 hours of hypoxia followed by 4 hours of reoxygenation (H/R). Cell viability (a), LDH release (b), 15-F2t-isoprostane (15-F2t-IsoP) (c), representative Western blot of Cav-3 compared with GADPH (d), p-Akt (ser473) compared with total Akt (e), and p-STAT3 (Tyr705) compared with total STAT3 (f). All these results are expressed as ,. Differences were determined by one-way ANOVA followed by Tukey’s test. and vs. the HG+H/R group; vs. the HG+H/R+NAC group; and vs. the HG+H/R+NAC+Remi group.