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相思豆蛇毒对血管平滑肌细胞的影响：NADPH 氧化酶衍生的活性氧的贡献。

Effects of Lonomia obliqua Venom on Vascular Smooth Muscle Cells: Contribution of NADPH Oxidase-Derived Reactive Oxygen Species.

机构信息

Laboratório de Biologia RedOx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro CEP 21941-902, Brazil.

Laboratório de Farmacologia Celular e Molecular, Departamento de Biologia Celular, Universidade do Estado do Rio de Janeiro, Rio de Janeiro CEP 20550-030, Brazil.

出版信息

Toxins (Basel). 2017 Nov 7;9(11):360. doi: 10.3390/toxins9110360.

DOI:10.3390/toxins9110360
PMID:29112156
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5705975/
Abstract

Envenomation caused by human contact with the caterpillar Lonomia is characterized by deleterious effects on coagulation and patency of blood vessels. The cellular effects induced by venom highlights its capacity to activate endothelial cells, leading to a proinflammatory phenotype. Having more knowledge about the mechanisms involved in envenomation may contribute to better treatment. We aimed to evaluate the effects of caterpillar bristle extract (LOCBE) on vascular smooth muscle cells (VSMC). We observed that LOCBE induced VSMC migration, which was preceded by alterations in actin cytoskeleton dynamics and Focal Adhesion Kinase activation. LOCBE also induced Extracellular Signal-Regulated Kinase (ERK) phosphorylation in VSMC, and the inhibition of this pathway impaired cell proliferation. Stimulation of VSMC with LOCBE triggered reactive oxygen species (ROS) production through the activation of NADPH oxidase. The rapid increase in these ROS further induced mitochondrial ROS production, however only NADPH oxidase-derived ROS were involved in ERK activation in VSMC. We that demonstrated the chemotactic and proliferative effects of LOCBE on VSMC were dependent on ROS production, mainly through NADPH oxidase. Together, the data show that venom can interact with and activate VSMC. These effects rely on ROS production, suggesting new potential targets for treatment against vascular damage during envenomation.

摘要

由人类接触毛毛虫 Lonomia 引起的中毒表现为对凝血和血管通畅性的有害影响。毒液引起的细胞效应突出了其激活内皮细胞的能力，导致促炎表型。更多地了解中毒涉及的机制可能有助于更好地治疗。我们旨在评估毛毛虫毛鳞提取物（LOCBE）对血管平滑肌细胞（VSMC）的影响。我们观察到 LOCBE 诱导 VSMC 迁移，这是由肌动蛋白细胞骨架动力学和粘着斑激酶激活的改变引起的。LOCBE 还诱导 VSMC 中细胞外信号调节激酶（ERK）的磷酸化，而抑制该途径会损害细胞增殖。LOCBE 刺激 VSMC 会通过激活 NADPH 氧化酶来产生活性氧物质（ROS）。这些 ROS 的快速增加进一步诱导线粒体 ROS 的产生，但只有 NADPH 氧化酶衍生的 ROS 参与 VSMC 中的 ERK 激活。我们证明了 LOCBE 对 VSMC 的趋化和增殖作用依赖于 ROS 的产生，主要是通过 NADPH 氧化酶。总之，这些数据表明毒液可以与 VSMC 相互作用并激活 VSMC。这些作用依赖于 ROS 的产生，这表明在中毒期间针对血管损伤的治疗有新的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/ca0b13136999/toxins-09-00360-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/af41372c99ca/toxins-09-00360-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/cceb46fb3f6f/toxins-09-00360-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/afc8b994366e/toxins-09-00360-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/0901219413ae/toxins-09-00360-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/df21cb63271d/toxins-09-00360-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/12748b112a3c/toxins-09-00360-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/ca0b13136999/toxins-09-00360-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/af41372c99ca/toxins-09-00360-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/cceb46fb3f6f/toxins-09-00360-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/afc8b994366e/toxins-09-00360-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/0901219413ae/toxins-09-00360-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/df21cb63271d/toxins-09-00360-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/12748b112a3c/toxins-09-00360-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7122/5705975/ca0b13136999/toxins-09-00360-g007.jpg

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The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration.肌动蛋白细胞骨架、中间丝和微管在平滑肌细胞迁移中的作用及调控
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