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Antiangiogenic properties of BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cells.

التفاصيل البيبلوغرافية
العنوان: Antiangiogenic properties of BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cells.
المؤلفون: Oliveira VQ; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil., Santos LC; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil., Teixeira SC; Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia (UFU), Uberlândia, MG, Brazil. Electronic address: samuctx@gmail.com., Correia TML; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil., Andrade LOSB; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil., Gimenes SNC; Laboratory of Immunopathology, Institute of Butantan, São Paulo, SP, Brazil., Colombini M; Laboratory of Immunopathology, Institute of Butantan, São Paulo, SP, Brazil., Marques LM; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil., Jiménez-Charris E; Grupo de Nutrición, Facultad de Salud, Universidad Del Valle, Cali, Colombia., Freitas-de-Sousa LA; Laboratory of Immunopathology, Institute of Butantan, São Paulo, SP, Brazil., Silva MJB; Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia (UFU), Uberlândia, MG, Brazil., Magalhães Gusmão ACM; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil., Ferro EAV; Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia (UFU), Uberlândia, MG, Brazil., Clissa PB; Laboratory of Immunopathology, Institute of Butantan, São Paulo, SP, Brazil., Melo Rodrigues V; Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlandia (UFU), Uberlândia-MG, Brazil., Lopes DS; Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil. Electronic address: lsdaiana@yahoo.com.br.
المصدر: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Apr 30; Vol. 706, pp. 149748. Date of Electronic Publication: 2024 Mar 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Endothelial Cells*/metabolism , Bothrops*/metabolism , Venomous Snakes*, Animals ; Female ; Humans ; Vascular Endothelial Growth Factor A/metabolism ; Metalloproteases/metabolism ; Snake Venoms ; Human Umbilical Vein Endothelial Cells/metabolism ; Angiogenesis Inhibitors/pharmacology
مستخلص: Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 μg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 μg/mL, respectively, and the number of tubules by 15.9 at 5 μg/mL and 21.6 at 40 μg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 μg/mL and by 66% at 40 μg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Antiangiogenic effects and VEGF pathway; Metalloproteinase; Snake venom
المشرفين على المادة: 0 (Vascular Endothelial Growth Factor A)
EC 3.4.- (Metalloproteases)
0 (Snake Venoms)
0 (Angiogenesis Inhibitors)
SCR Organism: Bothrops moojeni
تواريخ الأحداث: Date Created: 20240309 Date Completed: 20240325 Latest Revision: 20240325
رمز التحديث: 20240325
DOI: 10.1016/j.bbrc.2024.149748
PMID: 38460450
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2104
DOI:10.1016/j.bbrc.2024.149748