Snake Venom Cytotoxins, Phospholipase A(2)s, and Zn(2+)-dependent Metalloproteinases: Mechanisms of Action and Pharmacological Relevance.
Snake Venom Cytotoxins, Phospholipase A(2)s, and Zn(2+)-dependent Metalloproteinases: Mechanisms of Action and Pharmacological Relevance.
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DOI：
10.4172/2161-0495.1000181
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发表时间：
2014-01-25
期刊：
影响因子：
--
通讯作者：
Rael ED
中科院分区：
文献类型：
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作者：
Gasanov SE;Dagda RK;Rael ED
蛇毒毒素是导致蛇毒中毒后严重病理和毒性的原因，包括坏死、凋亡、神经毒性、肌毒性、心脏毒性、大量出血和血液稳态破坏。因此，在临床上，蛇毒毒素对蛇咬伤的受害者是一个重大的危险，这强调了生产更有效的抗蛇毒血清的必要性。然而，一些蛇毒毒素作为治疗人类疾病的药物具有很大的潜力。本文综述了蛇毒毒素对人体组织的生物化学、结构/功能和病理学影响。我们提供了一个广泛的概述眼镜蛇毒细胞毒素，催化活性和非活性磷脂酶A2 s（PLA 2s），和Zn 2+依赖的金属蛋白酶。我们还提出了生物医学应用，蛇毒毒素可用于治疗人类疾病。例如，眼镜蛇毒细胞毒素可以用作抗癌剂，因为它们在破坏某些类型的癌细胞（包括白血病）方面是有效的。此外，增加我们对蛇毒PLA 2促进细胞膜磷脂水解的分子机制的理解，可以深入了解治疗由内源性PLA 2活性失调引起的自身免疫性疾病的潜在生物医学意义。最后，我们提供了一个详尽的概述蛇毒锌2+依赖性金属蛋白酶，并建议这些酶可以被工程化治疗深静脉血栓形成和神经退行性疾病的方法。
Snake venom toxins are responsible for causing severe pathology and toxicity following envenomation including necrosis, apoptosis, neurotoxicity, myotoxicity, cardiotoxicity, profuse hemorrhage, and disruption of blood homeostasis. Clinically, snake venom toxins therefore represent a significant hazard to snakebite victims which underscores the need to produce more efficient anti-venom. Some snake venom toxins, however, have great potential as drugs for treating human diseases. In this review, we discuss the biochemistry, structure/function, and pathology induced by snake venom toxins on human tissue. We provide a broad overview of cobra venom cytotoxins, catalytically active and inactive phospholipase A2s (PLA2s), and Zn2+-dependent metalloproteinases. We also propose biomedical applications whereby snake venom toxins can be employed for treating human diseases. Cobra venom cytotoxins, for example, may be utilized as anti-cancer agents since they are efficient at destroying certain types of cancer cells including leukemia. Additionally, increasing our understanding of the molecular mechanism(s) by which snake venom PLA2s promote hydrolysis of cell membrane phospholipids can give insight into the underlying biomedical implications for treating autoimmune disorders that are caused by dysregulated endogenous PLA2 activity. Lastly, we provide an exhaustive overview of snake venom Zn2+-dependent metalloproteinases and suggest ways by which these enzymes can be engineered for treating deep vein thrombosis and neurodegenerative disorders.