Mechanisms of chloride in cardiomyocyte anoxia-reoxygenation injury: the involvement of oxidative stress and NF-kappaB activation

During anoxia/reoxygenation (A/R) injury, intracellular chloride ion concentration ([Cl-](i)) homeostasis may play a role in maintaining the normal physiological function of cardiomyocytes. Various chloride transport systems could have influenced the concentration of chloride ion, but what kinds of chloride transport systems could play an important role in cardiomyocytes subjected to A/R injury and its mechanism are unknown. The aim of our study was to clarify the contributions of various chloride transport systems to anoxia/reoxygenation in rat neonatal cardiac myocytes and further to investigate the involved mechanisms. Oxidative stress and redox-sensitive transcription factor (NF-kappaB) activation are believed to play an important role in the A/R injury. To assess whether oxidative stress and NF-kappaB involve [Cl-](i) changes resulting in cardiomyocytes injury, the anoxia-reoxygenation (A/R) injury model was successfully established and administered with inhibitors of various chloride transport systems. Administration with Cl--substitution and Cl-/HCO3 (-) exchange inhibitor(SITS) has been shown to produce a protective effect against A/R injury by decreasing [Cl-](i) concentration, lipid peroxidation (malondialdehyde (MDA)) levels, and NF-kappaB activity, and by increasing antioxidant enzyme (glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase(CAT)) activity. However, inhibitors for the Cl--channel (9-AC) and Na+-K+-2Cl(-) co-transporter (bumetanide) had no effects. Our results indicate that Cl-/HCO3 (-) exchange system plays an important role in the cardiocyte A/R injury by influencing [Cl-](i) concentration. The protective effects of SITS and Cl--substitution on cardiomyocytes may be due to the attenuation of oxidative stress and inhibition of NF-kappaB activation.