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A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells

Title
A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells
Authors
Jang, Seung PilOh, Jae GyunKang, Dong HoonKang, Ju YoungKang, Sang WonHajjar, Roger J.Park, Woo Jin
Ewha Authors
강동훈
SCOPUS Author ID
강동훈scopus
Issue Date
2016
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 11, no. 10
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Neointimal growth in the injured vasculature is largely facilitated by the proliferation of vascular smooth muscle cells (VSMC), which associates with reduced sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. The gene transfer-mediated restoration of the SERCA2a level thus attenuates neointimal growth and VSMC proliferation. We previously reported that a peptide targeted to protein phosphatase 1, psi PLB-SE, normalizes SERCA2a activity in cardiomyocytes. In this study, we found that psi PLB-SE attenuated neointimal growth in balloon-injured rat carotid arteries, and the proliferation and migration of VSMC cultured in high-serum media (synthetic conditions). In parallel, psi PLB-SE inhibited the degradation of SERCA2a in the injured carotid arteries and VSMC under synthetic conditions. The calpain inhibitor MDL28170 also attenuated SERCA2a degradation and VSMC proliferation under synthetic conditions, indicating that calpain degrades SERCA2a. The Ca2+ ionophore A23187 induced SERCA2a degradation in VSMC, which was blocked by either psi PLB-SE or MDL28170. Additionally, psi PLB-SE normalized the cytosolic Ca2+ level in VSMC that was increased by either A23187 or synthetic stimulation. Collectively, these data indicate that psi PLB-SE corrects the abnormal Ca2+ handling by activating SERCA2a, which further protects SERCA2a from calpain-dependent degradation in VSMC. We conclude that psi PLB-SE may form the basis of a therapeutic strategy for vascular proliferative disorders.
DOI
10.1371/journal.pone.0165569
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연구기관 > 세포항상성연구센터 > Journal papers
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