Effect of heparin treatment on the expression and activity of different ion-motive P-type ATPase isoforms from mouse extensor digitorum longus muscle during degeneration and regeneration after Bothrops jararacussu venom injection |
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Authors: | Naiara Schaffazick Tatiane F Fonseca Glauco A Gaban Sabrina Calil-Elias Paulo A Melo Valéria MN Cunha |
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Institution: | a Programa de Farmacologia Celular e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS/ICB - Bl.J, sala J-17, Rio de Janeiro, RJ 21941-902, Brazil b Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil c Departamento de Farmácia e Administração Farmacêutica, Faculdade de Farmácia, Universidade Federal Fluminense, Niterói, RJ, Brazil |
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Abstract: | Ca2+ ions are essential to myonecrosis, a serious complication of snake envenomation, and heparin seems to counteract this effect. We investigated the effect of local injection of Bothrops jararacussu venom in mouse fast-twitch extensor digitorum longus (EDL) muscle, without or with heparin, on functional/molecular alterations of two central proteins involved in intracellular Ca2+ homeostasis, sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and Na+/K+-ATPase. EDL-specific SERCA1 isoform expression dropped significantly just after venom administration (up to 60% compared to control EDL values at days 1 and 3; p < 0.05) while SERCA2 and Na+/K+-ATPase α1 isoform expression increased at the same time (3-6- and 2-3-fold, respectively; p < 0.05). Although not significant, Na+/K+-ATPase α2 isoform followed the same trend. Except for SERCA2, all proteins reached basal levels at the 7th day. Intravenous heparin treatment did not affect these profiles. Ca2+-ATPase activity was also decreased during the first days after venom injection, but here heparin was effective to reinstate activity to control levels within 3 days. We also showed that B. jararacussu venom directly inhibited Ca2+-ATPase activity in a concentration-dependent manner. Our results indicate that EDL SERCA and Na+/K+-ATPase are importantly affected by B. jararacussu venom and heparin has protective effect on activity but not on protein expression. |
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Keywords: | Bothrops jararacussu Snake venom Myonecrosis Ca2+-ATPase Na+/K+-ATPase Heparin |
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