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

• Grant number: 12/10993-4
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2012
• Effective date (End): August 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Compared Physiology
• Principal Investigator: Francisco Tadeu Rantin
• Grantee: Diana Amaral Monteiro
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Recent studies have shown that alternagin-C (ALT-C), a disintegrin-like protein purified from the venom of the snake urutu (R. alternatus), is able to induce in vivo angiogenesis and in vitro endothelial cell proliferation and migration. This molecule, therefore, has potential to be used in the pharmaceutical industry, as an adjuvant to pro-angiogenic therapies that are essentials in cardiovascular diseases. The research project proposes an investigation about the effect of ALT-C on the fish myocardial contractility in order to investigate if this disintegrin acts positively on excitation-contraction coupling of the myocytes by inducing the angiogenesis and modulation of Ca2+ signaling pathways, improving contraction force, cardiac pumping capacity and hypoxia tolerance. The dose will be chosen after the detection of the dose-response relationship. For this purpose we will carry out purification of the protein from the lyophilized venom of B. alternatus through a double filtration followed by anion exchange chromatography. Fish will receive a single intravenous dose of ALT-C and after 7 days, the cardiac muscle contractility in vitro will be analyzed in normoxia or under hypoxia. We will also assess the quantification of vascular endothelial growth factor (VEGF) by ELISA assay; expression of excitation-contraction coupling proteins (Na+/Ca2+ exchanger; sarcoplasmic reticulum Ca2+-ATPase and phospholamban) by Western blot; coronary vasculature and collagen deposition by light microscopy; and imunohistochemical labeling of endothelial cells. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MONTEIRO, D. A.; KALININ, A. L.; SELISTRE-DE-ARAUJO, H. S.; NOGUEIRA, L. A. N.; BELETTI, M. E.; FERNANDES, M. N.; RANTIN, F. T.. Cardioprotective effects of alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom, on hypoxia-reoxygenation-induced injury in fish. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 215, p. 67-75, JAN 2019. (12/10993-4, 13/00798-2)

MONTEIRO, DIANA AMARAL; KALININ, ANA LUCIA; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; RANTIN, FRANCISCO TADEU. ormetic-like dose-response induced by alternagin-C, a protein isolated from urutu snake (Rhinocerophis alternatus) venom, in fish (Hoplias malabaricus) cardiac contractilit. Toxicon, v. 205, p. 67-70, JAN 2022. (13/00798-2, 12/10993-4)

MONTEIRO, DIANA AMARAL; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; TAVARES, DRIELE; FERNANDES, MARISA NARCISO; KALININ, ANA LUCIA; RANTIN, FRANCISCO TADEU. Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus. TOXINS, v. 9, n. 10, OCT 2017. (13/00798-2, 12/10993-4)

MONTEIRO, D. A.; KALININ, A. L.; SELISTRE-DE-ARAUJO, H. S.; VASCONCELOS, E. S.; RANTIN, F. T.. Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart. Toxicon, v. 110, p. 1-11, FEB 2016. (13/00798-2, 12/10993-4)