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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability
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Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability

机译：内皮细胞自噬的损害阻止了剪应力诱导的一氧化氮生物利用度的增加

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Autophagy is a lysosomal catabolic process by which cells degrade or recycle their contents to maintain cellular homeostasis, adapt to stress, and respond to disease. Impairment of autophagy in endothelial cells studied under static conditions results in oxidant stress and impaired nitric oxide (NO) bioavailability. We tested the hypothesis that vascular autophagy is also important for induction of NO production caused by exposure of endothelial cells to shear stress (i.e., 3 h x approximate to 20 dyn/cm(2)). Atg3 is a requisite autophagy pathway mediator. Control cells treated with non-targeting control siRNA showed increased autophagy, reactive oxygen species (ROS) production, endothelial NO synthase (eNOS) phosphorylation, and NO production upon exposure to shear stress (p < 0.05 for all). In contrast, cells with > 85% knockdown of Atg3 protein expression (via Atg3 siRNA) exhibited a profound impairment of eNOS phosphorylation, and were incapable of increasing NO in response to shear stress. Moreover, ROS accumulation and inflammatory cytokine production (MCP-1 and IL-8) were exaggerated (all p < 0.05) in response to shear stress. These findings reveal that autophagy not only plays a critical role in maintaining NO bioavailability, but may also be a key regulator of oxidant-antioxidant balance and inflammatory-anti-inflammatory balance that ultimately regulate endothelial cell responses to shear stress.
机译：自噬是溶酶体的分解代谢过程，通过该过程细胞降解或循环利用其内含物，以维持细胞稳态，适应压力并应对疾病。在静态条件下研究的内皮细胞自噬功能受损会导致氧化应激和一氧化氮（NO）生物利用度受损。我们测试了以下假设，即血管自噬对于诱导内皮细胞受到剪切应力（即3 h x约20 dyn / cm（2））引起的NO产生也很重要。 Atg3是必需的自噬途径介体。用非靶向对照siRNA处理的对照细胞显示增加的自噬，活性氧（ROS）产生，内皮一氧化氮合酶（eNOS）磷酸化和暴露于剪切应力时的一氧化氮产生（所有p均<0.05）。相比之下，Atg3蛋白表达（通过Atg3 siRNA）抑制率> 85％的细胞表现出eNOS磷酸化的严重损害，并且无法响应剪切应力而增加NO。此外，响应剪切应力，ROS积累和炎性细胞因子产生（MCP-1和IL-8）被夸大（所有p <0.05）。这些发现表明自噬不仅在维持NO生物利用度中起关键作用，而且可能是氧化剂-抗氧化剂平衡和炎症-抗炎平衡的关键调节剂，最终调节内皮细胞对切应力的反应。

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