Iron loading of cultured cardiac myocytes modifies sarcolemmal structure and increases lysosomal fragility

Gabriela Link, Arie Pinson, Chaim Hershko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The mechanism of damage to myocardial subcellular organelles was studied in iron-loaded rat myocardial cells in culture in an attempt to identify the primary target of iron's toxic effects. Lysosomes and sarcolemmal membranes were purified by fractionation of the postnuclear supernatant on a 6.7% colloidal polyvinylpyrrolidone-coated silica gradient. After 24-hour incubation with ferric ammonium citrate at a concentration of 20 μg/ml (0.36 mmol/L) iron, a selective depletion of polyunsaturated fatty acids was found in whole-cell homogenates, as well as in the postnuclear supernatant and sediment. Iron loading resulted in a sharp increase in the total activity of the lysosomal enzyme β-hexosaminidase in unfractionated whole-cell homogenates, increased free enzyme activity, and loss of latent activity indicating increased lysosomal fragility. Conversely, iron loading resulted in a marked decrease in the activity of the sarcolemmal enzyme 5′-nucleotidase and a significant loss of total protein sulfhydryl group content. These studies in cultured heart cells are in agreement with previous observations indicating increased lysosomal fragility in iron-loaded hepatic and splenic tissues, attributed to increased membrane lipid peroxidatlon. In addition, the marked decrease in sarcolemmal 5′-nucleotidase activity and in total protein sulfhydryl group content imply that iron-induced peroxidative damage to membrane proteins may be a more important mechanism in the pathogenesis of altered myocardial function in the iron-loaded heart than formerly was recognized.

Original languageAmerican English
Pages (from-to)127-134
Number of pages8
JournalTranslational Research
Volume121
Issue number1
StatePublished - Jan 1993

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