Overexpression of PEP-19 Suppresses Angiotensin II–Induced Cardiomyocyte Hypertrophy

Abstract

Abstract. The precise molecular mechanisms leading to disturbance of Ca 2+ /calmodulin dependent intracellular signalling in cardiac hypertrophy remains unclear. As an endogenous calmodulin regulator protein, the pathophysiology role of PEP19 during cardiac hypertrophy was investigated in the present study. We here demonstrated that PEP19 protein levels are significantly elevated in the aortic banding model in vivo and angiotensin II-induced cardio myocyte hypertrophy in vitro. Consistent with inhibitory actions of PEP19 on cardiomyocyte hypertrophy, induction of CaMKII and calcineurin activation as well as hypertrophyrelated genes including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was significantly inhibited by PEP19 transfection. Moreover, PEP19 partially ameliorates angiotensin II-induced elevation of phosphophospholamban (Thr17) and sarcoplasmic reticulum Ca 2+ release in cardiomyocytes. Together, our results suggest that PEP19 attenuates angiotensin II-induced cardiomyocyte hypertrophy via suppressing the disturbance of CaMKII and calcineurin signaling.

VEGFB‐VEGFR1 ameliorates Ang II‐induced cardiomyocyte hypertrophy through Ca2+‐mediated PKG I pathway

“…In addition to Ang II, calcineurin‐NFAT signaling channel is also significant for cardiac hypertrophy, in which Ca 2+ is required . After Ang II stimulation, Ca 2+ content could be significantly increased in cardiomyocyte . By inhibiting the Ca 2+ /Calcineurin‐NFAT signaling pathway, Angiotensin II‐induced cardiomyocyte hypertrophy could be attenuated .…”

“…7 After Ang II stimulation, Ca 2+ content could be significantly increased in cardiomyocyte. 8,9 By inhibiting the Ca 2+ /Calcineurin-NFAT signaling pathway, Angiotensin II-induced cardiomyocyte hypertrophy could be attenuated. 9 These data inspired us to hypothesize that to inhibit Ang IIstimulated Ca 2+ content and/or Ca 2+ -related pathway (s) could be an essential strategy for cardiomyocyte hypertrophy.…”

Expression, Regulation, and Function of the Calmodulin Accessory Protein PCP4/PEP-19 in Myometrium

“…The results of prior studies indicate a function for PCP4/PEP-19 in Ca 2þ homeostasis by modifying agonist-induced Ca 2þ release. 11,17,47 Here, we explored the potential role of PCP4/PEP-19 in maintaining quiescence by regulating agonist-induced Ca 2þ mobilization. Myometrial cells respond to uterotonic stimuli such as oxytocin by activating signaling cascades, leading to changes in intracellular Ca 2þ levels, which in turn, through the regulation of Ca 2þ -CaM, affects various cellular processes including the activity of the actin-myosin contractile apparatus.…”

“…For example, PCP4/ PEP-19 levels were increased in cerebellum of patients with Alzheimer disease 13 but decreased in the prefrontal cortex of alcoholics 14 and the basal ganglia in Huntington disease 15 and in a mouse model for Parkinson disease. 16 PCP4/PEP-19 was also induced in models of cardiac hypertrophy 17 and altered in several cancers. [18][19][20][21][22] At the cellular level, PCP4/PEP-19 has broad effects on diverse processes, including neurite outgrowth, 23 premature neuronal differentiation, 24 long-term plasticity at neuronal synapses, 25 altered cardiac excitability and contractility, 26 and antiapoptotic activity.…”

“…For example, PCP4/PEP-19 levels were increased in cerebellum of patients with Alzheimer disease 13 but decreased in the prefrontal cortex of alcoholics 14 and the basal ganglia in Huntington disease 15 and in a mouse model for Parkinson disease. 16 PCP4/PEP-19 was also induced in models of cardiac hypertrophy 17 and altered in several cancers. 18 -22…”