Differential effects of the venoms of Russell's viper and Indian cobra on human myoblasts
Differential effects of the venoms of Russell's viper and Indian cobra on human myoblasts
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DOI：
10.1038/s41598-024-53366-9
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发表时间：
2024-02-07
影响因子：
4.6
通讯作者：
Patel，Ketan
中科院分区：
文献类型：
--
作者：
Bin Haidar，Husain;Almeida，Jose R.;Patel，Ketan
蛇咬伤后的局部组织损伤仍然是一个研究不足的领域。为了开发更好的策略来治疗蛇咬伤，关键是要了解毒液毒素通过其诱导毒液蛰入效应包括局部组织损伤的机制。在这里，我们演示了如何使用培养的人成肌细胞系的毒液的两个医学上重要的印度蛇（罗素蝰蛇和眼镜蛇）影响人类骨骼肌。数据表明，这两种毒液影响成肌细胞的活力。拉塞尔蝰蛇毒液减少了细胞的总数，它们的迁移，以及局灶性粘连的面积。它还抑制肌源性分化和诱导肌肉萎缩。虽然眼镜蛇毒液降低了细胞的活力，但它并没有在很大程度上影响细胞迁移和粘着斑。眼镜蛇毒影响肌管的形成并引起萎缩。小分子抑制剂如伐瑞拉迪（一种磷脂酶A2抑制剂）和普利诺司他（一种金属蛋白酶抑制剂）以及可溶性激活素Ⅱ b型受体（一种用于促进骨骼肌再生的分子）不能逆转眼镜蛇毒液诱导的萎缩，尽管抗蛇毒血清（针对印度“四大”蛇）减弱了这种作用。然而，所有这些分子都拯救了拉塞尔蝰蛇毒液引起的肌管萎缩。这项研究展示了肌肉再生过程中的关键步骤，这些步骤受到印度罗素蝰蛇和眼镜蛇毒液的影响，并提供了对中毒受害者临床特征的潜在原因的见解。需要进一步的研究，以调查在体内环境下的蛇毒诱导的肌肉毒性的分子机制，并开发更好的治疗蛇咬伤引起的肌肉损伤。
Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell’s viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian ‘Big Four’ snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell’s viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell’s viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.