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QUESTION 45 Answer the following question in no more than 2 well-written sentences. Explain how inhibiting...

QUESTION 45

  1. Answer the following question in no more than 2 well-written sentences.

    Explain how inhibiting protein phosphatase 1 (PPI) with gene therapy can improve heart function for non-ischemic heart disease.

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Increased protein phosphatase-1 in heart failure (HF) induces molecular changes deleterious to the cardiac cell. Inhibiting protein phosphatase-1 through the overexpression of a constitutively active inhibitor-1 (I-1c) has been shown to reverse cardiac dysfunction in a model of ischemic HF.Disruption of Ca2+ homeostasis is a key pathomechanism in heart failure. CaMKII‐dependent hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown.

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