J Korean Med Sci.  2016 Apr;31(4):535-541. 10.3346/jkms.2016.31.4.535.

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

• Ha TS
• Park HY
• Seong SB
• Ahn HY

• KMID: 2363691
• DOI: http://doi.org/10.3346/jkms.2016.31.4.535

Abstract

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.

Keyword

AMP-activated Protein Kinase; Angiotensin II; p130Cas; Podocyte; Angiotensin II Type 1 Receptor

MeSH Terms

AMP-Activated Protein Kinases/antagonists & inhibitors/chemistry/*metabolism
Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
Angiotensin II/*pharmacology
Angiotensin II Type 1 Receptor Blockers/pharmacology
Animals
Blotting, Western
Cell Line
Cell Nucleus/metabolism
Crk-Associated Substrate Protein/*metabolism
Cytoplasm/metabolism
Focal Adhesion Kinase 1/metabolism
Losartan/pharmacology
Metformin/pharmacology
Mice
Microscopy, Confocal
Podocytes/cytology/drug effects/metabolism
Protein Kinase Inhibitors/*pharmacology
Ribonucleotides/pharmacology
Signal Transduction/*drug effects
AMP-Activated Protein Kinases
Aminoimidazole Carboxamide
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Crk-Associated Substrate Protein
Focal Adhesion Kinase 1
Losartan
Metformin
Protein Kinase Inhibitors
Ribonucleotides