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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase

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Author(s):
Freitas-de-Sousa, Luciana Aparecida ; Colombini, Monica ; Lopes-Ferreira, Monica ; Serrano, Solange M. T. ; Moura-da-Silva, Ana Maria
Total Authors: 5
Document type: Journal article
Source: TOXINS; v. 9, n. 8 AUG 2017.
Web of Science Citations: 12
Abstract

Hemorrhage is the most prominent effect of snake venom metalloproteinases (SVMPs) in human envenomation. The capillary injury is a multifactorial effect caused by hydrolysis of the components of the basement membrane (BM). The PI and PIII classes of SVMPs are abundant in viperid venoms and hydrolyze BM components. However, hemorrhage is associated mostly with PIII-class SVMPs that contain non-catalytic domains responsible for the binding of SVMPs to BM proteins, facilitating enzyme accumulation in the tissue and enhancing its catalytic efficiency. Here we report on Atroxlysin-Ia, a PI-class SVMP that induces hemorrhagic lesions in levels comparable to those induced by Batroxrhagin (PIII-class), and a unique SVMP effect characterized by the rapid onset of dermonecrotic lesions. Atroxlysin-Ia was purified from B. atrox venom, and sequence analyses indicated that it is devoid of non-catalytic domains and unable to bind to BM proteins as collagen IV and laminin in vitro or in vivo. The presence of Atroxlysin-Ia was diffuse in mice skin, and localized mainly in the epidermis with no co-localization with BM components. Nevertheless, the skin lesions induced by Atroxlysin-Ia were comparable to those induced by Batroxrhagin, with induction of leukocyte infiltrates and hemorrhagic areas soon after toxin injection. Detachment of the epidermis was more intense in skin injected with Atroxlysin-Ia. Comparing the catalytic activity of both toxins, Batroxrhagin was more active in the hydrolysis of a peptide substrate while Atroxlysin-Ia hydrolyzed more efficiently fibrin, laminin, collagen IV and nidogen. Thus, the results suggest that Atroxlysin-Ia bypasses the binding step to BM proteins, essential for hemorrhagic lesions induced by PII- and P-III class SVMPs, causing a significantly fast onset of hemorrhage and dermonecrosis, due to its higher proteolytic capacity on BM components. (AU)

FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 14/26058-8 - Inhibition of mammalian and snake venom metalloproteinases by the recombinant pro-domain of jararhagin and its relevant peptide fragments
Grantee:Ana Maria Moura da Silva
Support type: Regular Research Grants
FAPESP's process: 16/50127-5 - Dimensions US-BIOTA São Paulo: scales of biodiversity: integrated studies of snake venom evolution and function across multiple levels of diversity
Grantee:Inácio de Loiola Meirelles Junqueira de Azevedo
Support type: BIOTA-FAPESP Program - Thematic Grants