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

• Published in: Toxicon (Oxford) Vol. 55; no. 6; pp. 1071 - 1079
• Main Authors: Ellis, C.E., Naicker, D., Basson, K.M., Botha, C.J., Meintjes, R.A., Schultz, R.A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.06.2010; Elsevier
• Subjects: Actin; Actins - drug effects; Actins - metabolism; Animal poisons toxicology. Antivenoms; Animals; Animals, Newborn; Biological and medical sciences; Cardiotoxicity; Cells, Cultured; Connectin; Cytoskeletal Proteins - drug effects; Cytoskeletal Proteins - metabolism; Cytoskeleton; F-actin; Gousiekte; Medical sciences; Microscopy, Electron, Transmission; Muscle Proteins - drug effects; Muscle Proteins - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Myosin; Myosins - drug effects; Myosins - metabolism; Pavetamine; Polyamine; Polyamines - toxicity; Protein Kinases - drug effects; Protein Kinases - metabolism; Rat neonatal cardiomyocytes; Rats; Rats, Sprague-Dawley; Ruminantia; Sarcomeres - drug effects; Sarcomeres - ultrastructure; Titin; Toxicology; Tubulin - drug effects; Tubulin - metabolism; PBS; RNCM; Polyamine; PQC; MHC; SR/ER; Cardiotoxicity; Gousiekte; Rat neonatal cardiomyocytes; BSA; DMEM; LDH; LSCM; F-actin; Actin; Titin; Myosin; MURF; Cytoskeleton; Pavetamine; TEM; Neonatal; Rat; Toxicity; Rodentia; Contractile protein; Cardiovascular disease; Exposure; Vertebrata; Mammalia; Animal; Cardiomyocyte; Heart disease
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2009.12.006

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 β-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”.