2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice.
2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice.
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DOI：
10.1371/journal.pone.0189948
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Nakayama H
中科院分区：
文献类型：
--
作者：
Morihara H;Obana M;Tanaka S;Kawakatsu I;Tsuchiyama D;Mori S;Suizu H;Ishida A;Kimura R;Tsuchimochi I;Maeda M;Yoshimitsu T;Fujio Y;Nakayama H
活性氧 (ROS) 水平过高和 Ca2+ 稳态受损在多种心脏病的发生中发挥着重要作用，包括缺血再灌注 (I/R) 损伤期间的细胞死亡。在多个器官中，2-氨基乙氧基二苯基硼酸盐 (2-APB) 治疗显示出具有保护作用，通常认为这是由于 Ca2+ 通道抑制所致。然而，2-APB 诱导心脏保护的机制尚未得到充分研究。在此，我们研究了 2-APB 治疗对心脏发病机制的保护作用并破译了潜在的机制。在新生大鼠心肌细胞中，2-APB 治疗可通过抑制细胞内 Ca2+ 水平的增加来防止过氧化氢 (H2O2) 诱导的细胞死亡。然而，没有任何 2-APB 敏感通道阻滞剂能够抑制 H2O2 诱导的细胞死亡，并且 1H-NMR 检测到 2-APB 和 H2O2 之间存在直接反应，这表明 2-APB 通过化学方式清除细胞外 ROS 并提供细胞保护。在小鼠 I/R 模型中，2-APB 治疗可显着减少 I/R 后的梗塞面积，同时伴随着 ROS 水平和中性粒细胞浸润的减少，表明 2-APB 的抗氧化特性在预防体内 I/R 损伤中也发挥着重要作用。综上所述，目前的结果表明，2-APB 治疗至少部分通过直接清除细胞外 ROS 来诱导心脏保护并防止 ROS 诱导的心肌细胞死亡。因此，2-APB 的给药可能是治疗 ROS 相关心脏病（包括 I/R 损伤）的一种有前途的治疗策略。
Excessive levels of reactive oxygen species (ROS) and impaired Ca2+ homeostasis play central roles in the development of multiple cardiac pathologies, including cell death during ischemia-reperfusion (I/R) injury. In several organs, treatment with 2-aminoethoxydiphenyl borate (2-APB) was shown to have protective effects, generally believed to be due to Ca2+ channel inhibition. However, the mechanism of 2-APB-induced cardioprotection has not been fully investigated. Herein we investigated the protective effects of 2-APB treatment against cardiac pathogenesis and deciphered the underlying mechanisms. In neonatal rat cardiomyocytes, treatment with 2-APB was shown to prevent hydrogen peroxide (H2O2) -induced cell death by inhibiting the increase in intracellular Ca2+ levels. However, no 2-APB-sensitive channel blocker inhibited H2O2-induced cell death and a direct reaction between 2-APB and H2O2 was detected by 1H-NMR, suggesting that 2-APB chemically scavenges extracellular ROS and provides cytoprotection. In a mouse I/R model, treatment with 2-APB led to a considerable reduction in the infarct size after I/R, which was accompanied by the reduction in ROS levels and neutrophil infiltration, indicating that the anti-oxidative properties of 2-APB plays an important role in the prevention of I/R injury in vivo as well. Taken together, present results indicate that 2-APB treatment induces cardioprotection and prevents ROS-induced cardiomyocyte death, at least partially, by the direct scavenging of extracellular ROS. Therefore, administration of 2-APB may represent a promising therapeutic strategy for the treatment of ROS-related cardiac pathology including I/R injury.
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DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
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影响因子：
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发表时间：
1999-12-01
影响因子：
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