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.
Ca(2+) 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 Ca(2+) homeostasis, sarco(endo)plasmic reticulum Ca(2+)-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 alpha(1) isoform expression increased at the same time (3-6- and 2-3-fold, respectively; p<0.05). Although not significant, Na(+)/K(+)-ATPase alpha(2) 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. Ca(2+)-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 Ca(2+)-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.
Schaffazick
Naiara
N
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.
Amaral
Luciana S
LS
Fonseca
Tatiane F
TF
Tomaz
Marcelo A
MA
Gaban
Glauco A
GA
Borges
Paula A
PA
Calil-Elias
Sabrina
S
Noël
François
F
Melo
Paulo A
PA
Quintas
Luis Eduardo M
LE
Cunha
Valéria M N
VM
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D013045:Species Specificity; D013997:Time Factors
D000997:Antivenins; D003435:Crotalid Venoms; D007527:Isoenzymes; D006493:Heparin; D000251:Adenosine Triphosphatases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases