Toxicol In Vitro. 1998 Jun 01;12(3):233-40. doi: 10.1016/s0887-2333(97)00116-1.

Mechanism of polyamine toxicity in cultured cardiac myocytes.

Toxicology in vitro : an international journal published in association with BIBRA

U R Tipnis, G Y He

PMID: 20654405 DOI: 10.1016/s0887-2333(97)00116-1

Abstract

The goal of this study was to investigate the mechanism of polyamine-mediated injury to the cardiac myocytes isolated from neonatal rat hearts. The myocytes, cultured in Dulbecco's minimal essential medium-1% foetal calf serum (FBS), were exposed to spermidine or spermine. The toxicity to myocytes was determined by (a) increased release of creatine kinase (CPK) into the media and (b) decline in cell viability or functional activity. Spermidine, above 10 mum, increased the release of CPK into media, decreased cell viability and decreased the functional activity of the myocytes. The FBS exhibited polyamine oxidase activity and semicarbazide-sensitive amine oxidase activity. Aminoguanidine, MDL72,527 or semicarbazide, are the inhibitors of amine oxidases, polyamine oxidase (PAO) and semicarbazide-sensitive amine oxidase (SSAO), respectively. The addition of these inhibitors to the medium protected the myocytes from spermidine toxicity. To determine whether myocyte PAO is involved in polyamine toxicity, we used horse serum that contained high SSAO activity and negligible PAO activity. The myocyte extracts had negligible SSAO activity but high PAO activity. When myocytes were cultured in horse serum in lieu of FBS, spermine caused toxicity at above 100 mum. In horse serum, MDL72,527 and semicarbazide protected the myocytes from spermine toxicity. These observations show that extracellular amine oxidases and myocyte PAO are significant in mediation of polyamine toxicity.

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• Journal Article