...
首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Nitric oxide and calcium signaling regulate myocardial tumor necrosis factor-alpha expression and cardiac function in sepsis.
【24h】

Nitric oxide and calcium signaling regulate myocardial tumor necrosis factor-alpha expression and cardiac function in sepsis.

机译:一氧化氮和钙信号调节败血症中的心肌肿瘤坏死因子-α表达和心脏功能。

获取原文
获取原文并翻译 | 示例
           

摘要

Myocardial tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is a critical inducer of myocardial dysfunction in sepsis. The purpose of this review is to summarize the mechanisms through which TNF-alpha production is regulated in cardiomyocytes in response to lipopolysaccharide (LPS), a key pathogen-associated molecular pattern (PAMP) in sepsis. These mechanisms include Nox2-containing NAD(P)H oxidase, phospholipase C (PLC)gamma1, and Ca2+ signaling pathways. Activation of these pathways increases TNF-alpha expression via activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). Conversely, activation of c-Jun NH2-terminal kinase 1 (JNK1) negatively regulates TNF-alpha production through inhibition of ERK1/2 and p38 MAPK activity. Interestingly, endothelial nitric oxide synthase (eNOS) promotes TNF-alpha expression by enhancing p38 MAPK activation, whereas neuronal NOS (nNOS) inhibits TNF-alpha production by reducing Ca2+-dependent ERK1/2 activity. Therefore, the JNK1 and nNOS inhibitory pathways represent a "brake" that limits myocardial TNF-alpha expression in sepsis. Further understanding of these signal transduction mechanisms may lead to novel pharmacological therapies in sepsis.
机译:心肌炎性坏死因子-α(TNF-alpha)是促炎细胞因子,是脓毒症中心肌功能障碍的重要诱因。这篇综述的目的是总结对脂多糖(LPS)(一种败血症中的关键病原体相关分子模式(PAMP))作出反应而调节心肌细胞中TNF-α产生的机制。这些机制包括含Nox2的NAD(P)H氧化酶,磷脂酶C(PLC)gamma1和Ca2 +信号通路。这些途径的激活通过细胞外信号调节激酶1和2(ERK1 / 2)和p38丝裂原激活的蛋白激酶(MAPK)的激活来增加TNF-α的表达。相反,c-Jun NH2末端激酶1(JNK1)的激活通过抑制ERK1 / 2和p38 MAPK活性来负调节TNF-α的产生。有趣的是,内皮一氧化氮合酶(eNOS)通过增强p38 MAPK激活来促进TNF-α表达,而神经元NOS(nNOS)通过降低Ca2 +依赖性ERK1 / 2活性来抑制TNF-α的产生。因此,JNK1和nNOS抑制途径代表了一种“刹车”,它限制了败血症中心肌TNF-α的表达。对这些信号转导机制的进一步了解可能会导致败血症的新型药理疗法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号