title: Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart.
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 traíra, 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 Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo, Brazil. Electronic address: dianaamonteiro@yahoo.com.br.
authors.forename: D A
authors.initials: DA
authors.lastname: Monteiro
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Kalinin
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: H S
authors.initials: HS
authors.lastname: Selistre-de-Araujo
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: E S
authors.initials: ES
authors.lastname: Vasconcelos
authors.affiliation: Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: F T
authors.initials: FT
authors.lastname: Rantin
mesh_terms: D000818:Animals; D017756:Aquaculture; D017837:Bothrops; D002135:Calcium-Binding Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D060125:Characiformes; D003435:Crotalid Venoms / Q000737:chemistry; D019483:Disintegrins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D029941:Fish Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007269:Injections, Intra-Arterial; D009200:Myocardial Contraction / Q000187:drug effects*; D011897:Random Allocation; D030162:Reptilian Proteins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D016276:Ventricular Function / Q000187:drug effects; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D003435:Crotalid Venoms; D019483:Disintegrins; D029941:Fish Proteins; D030162:Reptilian Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D042461:Vascular Endothelial Growth Factor A; D000099211:Phospholamban; C481346:alternagin-C
keywords: ALT-C; Heart function; Myocardial contractility; NCX; SERCA; VEGF