4.4 Article

Damage to some contractile and cytoskeleton proteins of the sarcomere in rat neonatal cardiomyocytes after exposure to pavetamine

Journal

TOXICON
Volume 55, Issue 6, Pages 1071-1079

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2009.12.006

Keywords

Actin; Cardiotoxicity; Cytoskeleton; F-actin; Gousiekte; Myosin; Pavetamine; Polyamine; Rat neonatal cardiomyocytes; Titin

Funding

  1. North-West Department of Agriculture, Conservation, Environment and Tourism
  2. Gauteng Department of Agriculture, Conservation and Environment (GDACE)
  3. Department of Paraclinical Sciences, University of Pretoria

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Pavetamine, a cationic polyamine, is a cardiotoxin that affects ruminants. The animals die of heart failure after a period of four to eight weeks following ingestion of the plants that contain pavetamine. This immunofluorescent study was undertaken in rat neonatal cardiomyocytes (RNCM) to label some of the contractile and cytoskeleton proteins after exposure to pavetamine for 48 h. Myosin and titin were degraded in the RNCM treated with pavetamine and the morphology of alpha-actin was altered, when compared to the untreated cells, while those of beta-tubulin seemed to be unaffected. F-actin was degraded, or even absent, in some of the treated cells. On an ultrastructural level, the sarcomeres were disorganized or disengaged from the Z-lines. Thus, all three contractile proteins of the rat heart were affected by pavetamine treatment, as well as the F-actin of the cytoskeleton. It is possible that these proteins are being degraded by proteases like the calpains and/or cathepsins. The consequence of pavetamine exposure is literally a broken heart. (C) 2009 Elsevier Ltd. All rights reserved.

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