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Age-associated decrease in the catalytic unit activity of rat myocardial adenylate cyclase.

S W O'Connor, P J Scarpace, I B Abrass

    Mechanisms of Ageing and Development
    |March 1, 1983
    PubMed
    Summary
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    Aging reduces adenylate cyclase activity in rat hearts due to decreased catalytic unit function, not N-protein levels. This age-related decline in cardiac enzyme activity is tissue-specific.

    Area of Science:

    • Biochemistry
    • Cardiology
    • Gerontology

    Background:

    • Adenylate cyclase activity diminishes in aged rat myocardium.
    • Previous studies showed no change in beta-adrenergic receptor number or affinity, but decreased enzyme activity stimulated by NaF and GppNHp.
    • This suggests a defect in either the N-protein or catalytic unit of adenylate cyclase.

    Purpose of the Study:

    • To pinpoint the specific component responsible for reduced adenylate cyclase activity in aging rat myocardium.
    • To investigate the roles of N-protein and catalytic unit in age-related cardiac enzyme decline.

    Main Methods:

    • Assessed N-protein activity by complementing N-protein deficient cyc- S49 mouse lymphoma cells with myocardial membrane extracts from rats of different ages.
    • Evaluated catalytic unit activity using forskolin stimulation of adenylate cyclase in myocardial membranes from young and old rats.

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  • Examined tissue specificity by comparing myocardial results with erythrocyte membranes.
  • Main Results:

    • Both N-protein activity and catalytic unit activity were found to be diminished with age in rat myocardium.
    • N-protein was present in excess relative to the catalytic unit.
    • Age-dependent loss of adenylate cyclase activity was specific to myocardial tissue, not observed in erythrocyte membranes.

    Conclusions:

    • The loss of catalytic unit activity, rather than N-protein, is the primary cause of reduced adenylate cyclase activity in aging rat myocardium.
    • The age-related decline in cardiac adenylate cyclase activity is a tissue-specific phenomenon.