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Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase

Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously foun...

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Autores principales: Ha, Tae-Sun, Park, Hye-Young, Seong, Su-Bin, Ahn, Hee-Yul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810335/
https://www.ncbi.nlm.nih.gov/pubmed/27051236
http://dx.doi.org/10.3346/jkms.2016.31.4.535
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author Ha, Tae-Sun
Park, Hye-Young
Seong, Su-Bin
Ahn, Hee-Yul
author_facet Ha, Tae-Sun
Park, Hye-Young
Seong, Su-Bin
Ahn, Hee-Yul
author_sort Ha, Tae-Sun
collection PubMed
description Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.
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spelling pubmed-48103352016-04-05 Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase Ha, Tae-Sun Park, Hye-Young Seong, Su-Bin Ahn, Hee-Yul J Korean Med Sci Original Article Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury. The Korean Academy of Medical Sciences 2016-04 2016-03-02 /pmc/articles/PMC4810335/ /pubmed/27051236 http://dx.doi.org/10.3346/jkms.2016.31.4.535 Text en © 2016 The Korean Academy of Medical Sciences. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Ha, Tae-Sun
Park, Hye-Young
Seong, Su-Bin
Ahn, Hee-Yul
Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
title Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
title_full Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
title_fullStr Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
title_full_unstemmed Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
title_short Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase
title_sort angiotensin ii modulates p130cas of podocytes by the suppression of amp-activated protein kinase
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810335/
https://www.ncbi.nlm.nih.gov/pubmed/27051236
http://dx.doi.org/10.3346/jkms.2016.31.4.535
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