首页> 外文期刊>The Journal of Nutritional Biochemistry >Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction intercellular communication by blocking phosphorylation of connexin 43 via the MEK/ERK signaling pathway
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Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction intercellular communication by blocking phosphorylation of connexin 43 via the MEK/ERK signaling pathway

机译:可可多酚通过阻断连接蛋白43通过MEK / ERK信号通路的磷酸化,减弱了过氧化氢对间隙连接细胞间通讯的抑制作用

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摘要

Cocoa, a good source of dietary antioxidative polyphenols, exhibited anticarcinogenic activity in animal models, but the molecular mechanisms of the chemopreventive potential of cocoa remain unclear. Inhibition of gap-junction intercellular communication (GJIC) is strongly related to tumorigenesis. Cocoa polyphenol extracts (CPE) dose dependently attenuated hydrogen peroxide (H2O2)-induced inhibition of GJIC in rat liver epithelial (RLE) cells. CPE inhibited the H2O2-induced phosphorylation and internalization of connexin 43, which is a regulating protein of GJIC in RLE cells. The H2O2-induced accumulation of reactive oxygen species and activation of extracellular signal-regulated kinase were inhibited by CPE treatment. However, CPE did not block H2O2-induced phosphorylation of p38 mitogen-activated protein kinase. An ex vivo kinase assay demonstrated that CPE inhibited the H2O2-induced mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 activity in RLE cell lysates. Ex vivo pull-down assay data revealed that CPE directly bound with MEK1 to inhibit MEK1 activity. These results indicate that CPE protects against the H2O2-induced inhibition of GJIC through antioxidant activity and direct inhibition of MEK activity, which may contribute to its chemopreventive potential
机译:可可是饮食中抗氧化多酚的良好来源,在动物模型中显示出抗癌活性,但可可化学预防潜力的分子机制仍不清楚。间隙连接细胞间通讯(GJIC)的抑制与肿瘤发生密切相关。可可多酚提取物(CPE)剂量依赖性地减弱了过氧化氢(H2O2)对大鼠肝上皮(RLE)细胞中GJIC的抑制作用。 CPE抑制H2O2诱导的连接蛋白43的磷酸化和内在化,连接蛋白43是RLE细胞中GJIC的调节蛋白。 CPE处理可抑制H2O2诱导的活性氧积累和细胞外信号调节激酶的激活。但是,CPE不能阻止H2O2诱导的p38丝裂原活化蛋白激酶的磷酸化。离体激酶测定表明,CPE抑制了RLE细胞裂解物中H2O2诱导的丝裂原激活的蛋白激酶/细胞外信号调节激酶激酶(MEK)1的活性。离体下拉测定数据显示CPE直接与MEK1结合以抑制MEK1活性。这些结果表明,CPE通过抗氧化剂活性和MEK活性的直接抑制作用来防止H2O2诱导的GJIC抑制作用,这可能有助于其化学预防潜力

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