Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart

Author(s)

Monteiro, D. A. ^[1] ; Kalinin, A. L. ^[1] ; Selistre-de-Araujo, H. S. ^[1] ; Vasconcelos, E. S. ^[1] ; Rantin, F. T. ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Physiol Sci, BR-13560 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Toxicon; v. 110, p. 1-11, FEB 2016.
• Web of Science Citations: 4

Abstract

Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traira, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca2+-cycling proteins such as SERCA (sarcoplasmic reticulum Ca2+-ATPase), PLB (phospholamban), and NCX (Na+/Ca2+ exchanger); 4) abolishment of the typical negative force frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca2+ handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/00798-2 - The extracellular matrix in aging, exercise and in the tumor microenvironment
• Grantee: Heloisa Sobreiro Selistre de Araújo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/10993-4 - Effects of alternagin-C (ALT-C), a protein from venom of urutu snake (Rhinocerophis alternatus, previously known Bothrops alternatus), on fish cardiac contractility under normoxia and against tissue hypoxia
• Grantee: Diana Amaral Monteiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral