Targeted proteolysis sustains calcineurin activation

Natalie Burkard, Jan Becher, Cornelia Heindl, Ludwig Neyses, Kai Schuh, Oliver Ritter

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background - Calcineurin (CnA) is important in the regulation of myocardial hypertrophy. We demonstrated that targeted proteolysis of the CnA autoinhibitory domain under pathological myocardial workload leads to increased CnA activity in human myocardium. Here, we investigated the proteolytic mechanism leading to activation of CnA. Methods and Results - In patients with diseased myocardium, we found strong nuclear translocation of CnA. In contrast, in normal human myocardium, there was a cytosolic distribution of CnA. Stimulation of rat cardiomyocytes with angiotensin (Ang) II increased calpain activity significantly (433±11%; P
    Original languageEnglish
    Pages (from-to)1045-1053
    Number of pages8
    JournalCirculation
    Volume111
    Issue number8
    DOIs
    Publication statusPublished - 1 Mar 2005

    Keywords

    • Calcium
    • Hypertrophy
    • Molecular biology
    • Myocardium

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