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Protein Half-life of Degradation Machineries in Healthy and Stressed Myocardium

  • Author(s): Polson, Jennifer Sara
  • Advisor(s): Watson, Rachelle H
  • Ping, Peipei
  • et al.

Protein synthesis and degradation function in concert to maintain myocardial proteome homeostasis and render proteome dynamics triggered by pathological stresses; mounting evidence documents their dysfunction as a cardiac disease driver. Despite our knowledge of hypertrophic signaling cascades in heart, little is known about the concomitant self-regulation of protein synthesis and degradation machineries during this proteome-wide remodeling. For 6 genetic mouse strains that developed distinguishable scales of ISO-induced hypertrophy, the basal and altered protein half-lives were quantified for proteasomal subunits as well as other degradation and synthesis machineries. Contractile proteins were quantified as half-life references to hypertrophy. The workflow developed in this study revealed the unique turnover features among six genetic strains, the distinct turnover modulation of individual proteasomal subunits under β-adrenergic stimulation, and a signature of contractile protein turnover alteration. Together with functional assessments, our discovery supports future investigations to dissect these regulatory processes in maladaptive cardiac remodeling.

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