Inhibition of calcium accumulatory by the sarcoplasmic reticulum: A putative mechanism for the cardiotoxicity of adriamycin

Irit Halili-Rutman, Chaim Hershko, Gavriela Link, Avram J. Rutman, Asher Shainberg

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    21 Scopus citations

    Abstract

    The aim of this study was to examine the effect of adriamycin (ADR) on calcium accumulation by the sarcoplasmic reticulum (SR). Chemical skinning of cultured rat myocardial cells compromised the barrier function of the cell membrane and thus permitted direct exposure of mitochondrial and non-mitochondrial sites to ADR. In the presence of ATP, and sodium azide, mitochondrial calcium accumulation was negligible. Furthermore, it has previously been shown that non mitochondrial calcium accumulation is mediated mainly by the SR under these conditions. Incubation with 10 μM ADR for 2 hr reduced the level of calcium accumulation by the SR by 50%. A similar effect was obtained after 24 hr incubation with 1 μM ADR. The addition of ferric iron to the culture medium further reduced the level of calcium accumulation. Neither vitamin E nor p carotene affected calcium accumulation by the SR. These results suggest that ADR interferes with the calcium accumulation activity of the SR and that ferric iron potentiates this effect.

    Original languageEnglish
    Pages (from-to)211-214
    Number of pages4
    JournalBiochemical Pharmacology
    Volume54
    Issue number1
    DOIs
    StatePublished - 1 Jul 1997

    Bibliographical note

    Funding Information:
    This study was supported by the joint Bar-Ifan-Shaare Zedek Research Foundation, and by Grant 93-22 from the united states Israel Bin&or& ScienceF oundation (BSP) , Jerusalem, Israel.

    Keywords

    • Adriamycin
    • Calcium accumulation
    • Cardiotoxicity
    • Iron
    • Reticulum
    • Sarcoplasmic

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