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探讨矛头蝮蛇毒液对大肠杆菌、绿脓杆菌和金黄色葡萄球菌以及 T47D 乳腺癌细胞的蛋白质谱和生物活性。

Exploring the protein profile and biological activity of Crotalus molossus venom against E. coli, P. aeruginosa and S. aureus bacteria and T47D breast carcinoma cells.

机构信息

Department of Research in Materials and Polymers, University of Sonora, Hermosillo, Sonora, 83000, Mexico.

Department of Health and Biological Sciences, University of Sonora, Hermosillo, Sonora, 83000, Mexico.

出版信息

Toxicon. 2024 Oct;249:108036. doi: 10.1016/j.toxicon.2024.108036. Epub 2024 Jul 24.

Abstract

Mexico has the highest diversity of snake species in the world, following Australia when considering just venomous snakes. Specifically, in Sonora, the second largest state in the country, more than 15 highly venomous species occur, including the northern black-tailed rattlesnake (Crotalus molossus). This specie's venom has not been as thoroughly researched in contrast with other Mexican vipers, nevertheless some studies report its biological activity and even pharmacological potential with antibacterial and cytotoxic activity. In this study we identified the main protein components from a pool of C. molossus venom through a gel-free proteomics approach, reporting ∼140 proteins belonging to the SVMP (38.76%), PLA (28.75%), CTL (11.93%), SVSP (6.03%) and LAAO (5.67%) toxin families. To study its biological activities, we evaluated its hemolytic, antibacterial, and cytotoxic activity in red blood cells, Gram positive and negative bacteria and a luminal A breast carcinoma cell line (T47D), respectively, in vitro. We report that concentrations <100 μg/mL are potentially not hemolytic and reduced the bacteria viability of E. coli and S. aureus with an IC of 10.27 and 11.51 μg/mL, respectively. Finally, we determined the C. molossus venom as cytotoxic against the T47D breast carcinoma cell line, with an IC of 1.55 μg/mL. We suggest that the evaluated cytotoxicity was due to a high abundance of SVMPs and PLAs, since it's been reported that they affect the extracellular matrix and membrane permeation. This may provide a useful tool for pharmaceutical screening in the future.

摘要

墨西哥拥有世界上最多样化的蛇种,在考虑毒蛇时仅次于澳大利亚。具体来说,在该国第二大州索诺拉,有超过 15 种剧毒蛇,包括北方黑尾响尾蛇(Crotalus molossus)。与其他墨西哥蝮蛇相比,这种蛇的毒液还没有被深入研究,但一些研究报告了它的生物活性,甚至具有抗菌和细胞毒性的药理学潜力。在这项研究中,我们通过无凝胶蛋白质组学方法从 C. molossus 毒液中鉴定出主要的蛋白质成分,报告了约 140 种属于 SVMP(38.76%)、PLA(28.75%)、CTL(11.93%)、SVSP(6.03%)和 LAAO(5.67%)毒素家族的蛋白质。为了研究其生物学活性,我们评估了其在红细胞、革兰氏阳性和阴性菌以及腔道 A 型乳腺癌细胞系(T47D)中的溶血、抗菌和细胞毒性活性,分别在体外进行。我们报告说,浓度<100μg/mL 可能没有溶血作用,并降低了大肠杆菌和金黄色葡萄球菌的细菌活力,IC 分别为 10.27 和 11.51μg/mL。最后,我们确定 C. molossus 毒液对 T47D 乳腺癌细胞系具有细胞毒性,IC 为 1.55μg/mL。我们认为,评估的细胞毒性是由于 SVMPs 和 PLAs 的高丰度所致,因为据报道它们会影响细胞外基质和膜渗透。这可能为未来的药物筛选提供有用的工具。

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