A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells.
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 neoin...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC5085086?pdf=render |
id |
doaj-e60a1c1bd2594e50bd4f1f72292f6d8e |
---|---|
record_format |
Article |
spelling |
doaj-e60a1c1bd2594e50bd4f1f72292f6d8e2020-11-25T00:40:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016556910.1371/journal.pone.0165569A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells.Seung Pil JangJae Gyun OhDong Hoon KangJu Young KangSang Won KangRoger J HajjarWoo Jin ParkNeointimal 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, ψPLB-SE, normalizes SERCA2a activity in cardiomyocytes. In this study, we found that ψPLB-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, ψPLB-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 ψPLB-SE or MDL28170. Additionally, ψPLB-SE normalized the cytosolic Ca2+ level in VSMC that was increased by either A23187 or synthetic stimulation. Collectively, these data indicate that ψPLB-SE corrects the abnormal Ca2+ handling by activating SERCA2a, which further protects SERCA2a from calpain-dependent degradation in VSMC. We conclude that ψPLB-SE may form the basis of a therapeutic strategy for vascular proliferative disorders.http://europepmc.org/articles/PMC5085086?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seung Pil Jang Jae Gyun Oh Dong Hoon Kang Ju Young Kang Sang Won Kang Roger J Hajjar Woo Jin Park |
spellingShingle |
Seung Pil Jang Jae Gyun Oh Dong Hoon Kang Ju Young Kang Sang Won Kang Roger J Hajjar Woo Jin Park A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. PLoS ONE |
author_facet |
Seung Pil Jang Jae Gyun Oh Dong Hoon Kang Ju Young Kang Sang Won Kang Roger J Hajjar Woo Jin Park |
author_sort |
Seung Pil Jang |
title |
A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. |
title_short |
A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. |
title_full |
A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. |
title_fullStr |
A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. |
title_full_unstemmed |
A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells. |
title_sort |
decoy peptide targeted to protein phosphatase 1 attenuates degradation of serca2a in vascular smooth muscle cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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, ψPLB-SE, normalizes SERCA2a activity in cardiomyocytes. In this study, we found that ψPLB-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, ψPLB-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 ψPLB-SE or MDL28170. Additionally, ψPLB-SE normalized the cytosolic Ca2+ level in VSMC that was increased by either A23187 or synthetic stimulation. Collectively, these data indicate that ψPLB-SE corrects the abnormal Ca2+ handling by activating SERCA2a, which further protects SERCA2a from calpain-dependent degradation in VSMC. We conclude that ψPLB-SE may form the basis of a therapeutic strategy for vascular proliferative disorders. |
url |
http://europepmc.org/articles/PMC5085086?pdf=render |
work_keys_str_mv |
AT seungpiljang adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT jaegyunoh adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT donghoonkang adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT juyoungkang adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT sangwonkang adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT rogerjhajjar adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT woojinpark adecoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT seungpiljang decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT jaegyunoh decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT donghoonkang decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT juyoungkang decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT sangwonkang decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT rogerjhajjar decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells AT woojinpark decoypeptidetargetedtoproteinphosphatase1attenuatesdegradationofserca2ainvascularsmoothmusclecells |
_version_ |
1725288316098576384 |