title: Mechanisms of chloride in cardiomyocyte anoxia-reoxygenation injury: the involvement of oxidative stress and NF-kappaB activation.
abstract: 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(-)/HCO(3) (-) 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(-)/HCO(3) (-) 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.
authors.affiliation: Jiangxi Provincial Institute of Hypertension at The First Affiliated Hospital, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: He
authors.forename: G L
authors.initials: GL
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Yin
authors.forename: Z P
authors.initials: ZP
authors.lastname: Liao
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.forename: Q R
authors.initials: QR
authors.lastname: Huang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Lai
authors.forename: M
authors.initials: M
authors.lastname: He
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D002034:Bumetanide / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D043302:Cultured Milk Products; D057075:Enzyme Assays; D005979:Glutathione Peroxidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D061251:Primary Cell Culture; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000873:Anthracenes; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C010030:9-anthroic acid; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010100:Oxygen