Effects of alternagin-C from Bothrops alternatus on gene expression and activity of metalloproteinases in regenerating skeletal muscle

Toxicon. 2008 Nov;52(6):687-94. doi: 10.1016/j.toxicon.2008.07.018. Epub 2008 Aug 9.

Abstract

This study evaluated the effects of alternagin-C (ALT-C) on mRNA levels of VEGF, MyoD and matrix metalloproteinase 2 (MMP-2) and on activity of MMPs in injured tibialis anterior (TA) muscle induced by cryolesioning in rats. Thirty-six Wistar rats (3 months old, 258.9+/-27 g) were divided into five groups: (1) control group; (2) injured TA and analyzed 3 days later; (3) injured TA treated with ALT-C and analyzed 3 days later; (4) injured TA and analyzed 7 days later and (5) injured TA treated with ALT-C and analyzed 7 days later. The injured muscle received 25 microl of ALT-C (50 nM). The injured and uninjured muscle areas were quantified by light microscopy. The MMP activity was evaluated through zymography, and mRNA of MyoD, VEGF and MMP-2 was assessed by quantitative polymerase chain reaction. ALT-C neither reduced the muscle injury area nor altered the pattern of MyoD and VEGF expression in injured muscles. However, ALT-C reduces both MMP-2 mRNA and gelatinolytic activity in injured muscles. The study indicates that ALT-C, at the tested concentrations, did not improve muscle regeneration process in rats. The effect on MMP-2 mRNA and gelatinolytic activity suggests that ALT-C changes the overall balance of ECM protein turnover during muscle regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bothrops*
  • Disintegrins / pharmacology*
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression / drug effects*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Metalloproteases / pharmacology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiology*
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*
  • Wound Healing / genetics

Substances

  • Disintegrins
  • MyoD Protein
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • alternagin-C
  • vascular endothelial growth factor A, rat
  • Metalloproteases
  • Matrix Metalloproteinase 2