Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability.
Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability.
复制标题
内皮细胞中自噬的损害可防止一氧化氮生物利用度的剪切压力诱导的增加。
DOI：
10.1139/cjpp-2014-0017
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发表时间：
2014-07
影响因子：
2.1
通讯作者：
Symons JD
中科院分区：
文献类型：
--
作者：
Bharath LP;Mueller R;Li Y;Ruan T;Kunz D;Goodrich R;Mills T;Deeter L;Sargsyan A;Anandh Babu PV;Graham TE;Symons JD
自噬是一种溶酶体分解代谢过程，通过该过程细胞降解或回收其内容物以维持细胞内稳态，适应压力和响应疾病。在静态条件下研究的内皮细胞自噬损伤导致氧化应激和受损的一氧化氮（NO）生物利用度。我们测试了血管自噬对于诱导内皮细胞暴露于剪切应力引起的NO产生也很重要的假设（即，3h × 120dyn/cm ~ 2）。atg 3是一种必需的自噬通路介质。用非靶向对照siRNA处理的对照细胞在暴露于剪切应力时显示出增加的自噬、活性氧（ROS）产生、内皮NO合酶（eNOS）磷酸化和NO产生（全部p < 0.05）。相比之下，Atg 3蛋白表达敲低>85%的细胞（通过Atg 3 siRNA）表现出eNOS磷酸化的严重损害，并且不能响应剪切应力增加NO。此外，响应于剪切应力，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生物利用度方面起着关键作用，而且可能是氧化-抗氧化平衡和炎症-抗炎平衡的关键调节剂，最终调节内皮细胞对剪切应力的反应。
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 × ≈20 dyn/cm2). 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.
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影响因子：
20.1
作者：
Symons JD;McMillin SL;Riehle C;Tanner J;Palionyte M;Hillas E;Jones D;Cooksey RC;Birnbaum MJ;McClain DA;Zhang QJ;Gale D;Wilson LJ;Abel ED
通讯作者：
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影响因子：
11.4
作者：
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影响因子：
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作者：
Chin, L. K.;Yu, J. Q.;Luo, K. Q.
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Luo, K. Q.
影响因子：
3.3
作者：
Ives, Stephen J.;Andtbacka, Robert H. I.;Richardson, Russell S.
通讯作者：
Richardson, Russell S.
影响因子：
11.4
作者：
Scherz-Shouval, Ruth;Shvets, Elena;Elazar, Zvulun
通讯作者：
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