Mechanisms of chloride in cardiomyocyte anoxia-reoxygenation injury: the involvement of oxidative stress and NF-kappaB activation
Mechanisms of chloride in cardiomyocyte anoxia-reoxygenation injury: the involvement of oxidative stress and NF-kappaB activation
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DOI：
10.1007/s11010-011-0855-9
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发表时间：
2011-05
影响因子：
4.3
通讯作者：
D. Liu;H. He;G. L. Li;J. Chen;D. Yin;Z. Liao;L. Tang;Q. Huang;Z. Lai;M. He
中科院分区：
文献类型：
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作者：
D. Liu;H. He;G. L. Li;J. Chen;D. Yin;Z. Liao;L. Tang;Q. Huang;Z. Lai;M. He
在缺氧/再氧化（A/R）损伤过程中，细胞内氯离子浓度（[Cl−]i）稳态可能在维持心肌细胞正常生理功能中发挥作用。不同的氯离子转运系统可能会影响氯离子的浓度，但哪种氯离子转运系统在A/R损伤心肌细胞中起重要作用及其机制尚不清楚。本研究的目的是阐明不同氯离子转运系统对大鼠新生心肌细胞缺氧/再氧化的作用，并进一步探讨其相关机制。氧化应激和氧化还原敏感转录因子（NF-kappaB）的激活被认为在A/R损伤中起重要作用。为了评估氧化应激和NF-kappaB是否参与[Cl−]变化导致心肌细胞损伤，我们成功建立了缺氧-再氧化（A/R）损伤模型，并给予各种氯离子运输系统抑制剂。使用Cl -取代和Cl - /HCO3 -交换抑制剂（sit）可以通过降低[Cl -]浓度、脂质过氧化（丙二醛（MDA））水平和NF-kappaB活性，以及增加抗氧化酶（谷胱甘肽过氧化物酶（GSHPx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT））活性，对a /R损伤产生保护作用。然而，Cl -通道（9-AC）和Na+ -K + -2Cl -共转运体（布美他尼）的抑制剂没有效果。结果表明，Cl−/HCO3−交换系统通过影响[Cl−]浓度在心肌细胞A/R损伤中起重要作用。sit和Cl -取代对心肌细胞的保护作用可能是由于氧化应激的衰减和NF-kappaB活化的抑制。
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−]ichanges 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−]iconcentration, 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−]iconcentration. 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.