Abstract
Aim:
To explore the mechanisms underlying the protection by SO2 preconditioning against rat myocardial ischemia/reperfusion (I/R) injury.
Methods:
Male Wistar rats underwent 30-min left coronary artery ligation followed by 120-min reperfusion. An SO2 donor (1 μmol/kg) was intravenously injected 10 min before the ischemia, while LY294002 (0.3 mg/kg) was intravenously injected 30 min before the ischemia. Plasma activities of LDH and CK were measured with an automatic enzyme analyzer. Myocardial infarct size was detected using Evans-TTC method. The activities of caspase-3 and -9 in myocardium were assayed using a commercial kit, and the levels of p-Akt, Akt, PI3K and p-PI3K were examined with Western blotting.
Results:
Pretreatment with SO2 significantly reduced the myocardial infarct size and plasma LDH and CK activities, as well as myocardial caspase-3 and -9 activities in the rats. Furthermore, the pretreatment significantly increased the expression levels of myocardial p-Akt and p-PI3K p85. Administration of the PI3K inhibitor LY294002 blocked all the effects induced by SO2 pretreatment.
Conclusion:
The results suggest that the PI3K/Akt pathway mediates the protective effects of SO2 preconditioning against myocardial I/R injury in rats.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Murry CE, Jennings RB, Reimer KA . Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 1124–36.
Toller WG, Kersten JR, Gross ER, Pagel PS, Warltier DC . Isoflurane preconditions myocardium against infarction via activation of inhibitory guanine nucleotide binding proteins. Anesthesiology 2000; 92: 1400–7.
Shapiro R . Genetic effects of bisulfite (sulfur dioxide). Mutat Res 1977; 39: 149–75.
Stipanuk MH, Dominy JE Jr, Lee JI, Coloso RM . Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J Nutr 2006; 136: 1652S–1659S.
Meng Z, Zhang B . Polymerase chain reaction-based deletion screening of bisulfite (sulfur dioxide)-enhanced gpt-mutants in CHO-AS52 cells. Mutat Res 1999; 425: 81–5.
Mottley C, Trice TB, Mason RP . Direct detection of the sulfur trioxide radical anion during the horseradish peroxidase-hydrogen peroxide oxidation of sulfite (aqueous sulfur dioxide). Mol Pharmacol 1982; 22: 732–7.
Reed GA, Ryan MJ, Adams KS . Sulfite enhancement of diolepoxide mutagenicity: the role of altered glutathione metabolism. Carcinogenesis 1990; 11: 1635–9.
Zhang RY, Du JB, Sun Y, Chen S, Tsai HJ, Yuan L, et al. Sulfur dioxide derivatives depress L-type calcium channel in rat cardiomyocytes. Clin Exp Pharmacol Physiol 2011; 38: 416–22.
Zhang S, Du J, Jin H, Li W, Liang Y, Geng B, et al. Endogenous sulfur dioxide aggravates myocardial injury in isolated rat heart with ischemia and reperfusion. Transplantation 2009; 87: 517–24.
Wang XB, Huang XM, Ochs T, Li XY, Jin HF, Tang CS, et al. Effect of sulfur dioxide preconditioning on rat myocardial ischemia/reperfusion injury by inducing endoplasmic reticulum stress. Basic Res Cardiol 2011; 106: 865–78.
Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM . Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol 2005; 289: H237–42.
Wymann MP, Zvelebil M, Laffargue M . Phosphoinositide 3–kinase signalling-which way to target? Trends Pharmacol Sci 2003; 24: 366–76.
Forster K, Paul I, Solenkova N, Staudt A, Cohen MV, Downey JM, et al. NECA at reperfusion limits infarction and inhibits formation of the mitochondrial permeability transition pore by activating p70S6 kinase. Basic Res Cardiol 2006; 101: 319–26.
Hu Y, Chen X, Pan TT, Neo KL, Lee SW, Khin ES, et al. Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K/Akt pathways. Pflugers Arch 2008; 455: 607–16.
Song JQ, Teng X, Cai Y, Tang CS, Qi YF . Activation of Akt/GSK-3beta signaling pathway is involved in intermedin (1–53) protection against myocardial apoptosis induced by ischemia/reperfusion. Apoptosis 2009; 14: 1299–307.
Zatta AJ, Kin H, Lee G, Wang N, Jiang R, Lust R, et al. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling. Cardiovasc Res 2006; 70: 315–24.
Elrod JW, Greer JJ, Bryan NS, Langston W, Szot JF, Gebregzlabher H, et al. Cardiomyocyte-specific overexpression of NO synthase-3 protects against myocardial ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 2006; 26: 1517–23.
Wei H, Zhang R, Jin H, Liu D, Tang X, Tang C, et al. Hydrogen sulfide attenuates hyperhomocysteinemia-induced cardiomyocytic endoplasmic reticulum stress in rats. Antioxid Redox Signal 2010; 12: 1079–91.
Zhang QN, Meng ZQ . The negative inotropic effects of gaseous sulfur dioxide and its derivatives in the isolated perfused rat heart. Environ Toxicol 2012; 27: 175–84.
Zhang QN, Meng ZQ . The vasodilator mechanism of sulfur dioxide on isolated aortic rings of rats: Involvement of the K+ and Ca2+ channels. Eur J Pharmacol 2009; 602: 117–23.
Bopassa JC, Ferrera R, Gateau-Roesch O, Couture-Lepetit E, Ovize M . PI3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning. Cardiovasc Res 2006; 69: 178–85.
Zhang CM, Gao L, Zheng YJ, Yang HT . Berbamine protects the heart from ischemia/reperfusion injury by maintaining cytosolic Ca2+ homeostasis and preventing calpain activation. Circ J 2012; 76: 1993–2002.
Izuishi K, Fujiwara M, Hossain MA, Usuki H, Maeta H . Significance of phosphoinositide 3-kinase pathway on ischemic preconditioning followed by ischemia reperfusion in mice liver. Transplant Proc 2003; 35: 132–3.
Matsui T, Li L, del Monte F, Fukui Y, Franke TF, Hajjar RJ, et al. Adenoviral gene transfer of activated phosphatidylinositol 3′-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation 1999; 100: 2373–9.
Matsui T, Tao J, del Monte F, Lee KH, Li L, Picard M, et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 2001; 104: 330–5.
Liang Y, Liu D, Ochs T, Tang C, Chen S, Zhang S, et al. Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats. Lab Invest 2011; 91: 12–23.
Lu Q, Zhai Y, Cheng Q, Liu Y, Gao X, Zhang T, et al. The Akt-FoxO3a-manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy. Exp Physiol 2012. DOI: 10.1113/expphysiol.2012.068361.
Wang Z, Zhang H, Xu X, Shi H, Yua X, Wang X, et al. bFGF inhibits ER stress induced by ischemic oxidative injury via activation of the PI3K/Akt and ERK1/2 pathways. Toxical Lett 2012; 212: 137–46.
Acknowledgements
This work was supported by the Major Basic Research Program of China (2012CB517806 and 2011CB503904) and the National Natural Science Foundation of China (81121061, 81070111, 31130030, and 81070212).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhao, Mm., Yang, Jy., Wang, Xb. et al. The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats. Acta Pharmacol Sin 34, 501–506 (2013). https://doi.org/10.1038/aps.2012.204
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2012.204
Keywords
This article is cited by
-
Near-infrared light-triggered nano-prodrug for cancer gas therapy
Journal of Nanobiotechnology (2021)
-
Mechanism of Human Umbilical Cord Mesenchymal Stem Cells Derived-Extracellular Vesicle in Cerebral Ischemia-Reperfusion Injury
Neurochemical Research (2021)
-
Short-term effects of ambient air pollutants and myocardial infarction in Changzhou, China
Environmental Science and Pollution Research (2018)
-
Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway
Acta Pharmacologica Sinica (2016)
-
The PI3K/Akt, p38MAPK, and JAK2/STAT3 signaling pathways mediate the protection of SO2 against acute lung injury induced by limb ischemia/reperfusion in rats
The Journal of Physiological Sciences (2016)
