title: Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase.
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.
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea .
authors.forename: Tae-Sun
authors.identifier: 0000-0002-1249-9342
authors.initials: TS
authors.lastname: Ha
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea .
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea .
authors.forename: Su-Bin
authors.initials: SB
authors.lastname: Seong
authors.affiliation: Department of Pharmacology, College of Medicine, Chungbuk National University, Cheongju, Korea .
authors.forename: Hee-Yul
authors.initials: HY
authors.lastname: Ahn
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D018613:Microscopy, Confocal; D050199:Podocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D050719:Crk-Associated Substrate Protein; D047428:Protein Kinase Inhibitors; D012265:Ribonucleotides; D000804:Angiotensin II; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D019808:Losartan
keywords: AMP-activated Protein Kinase; Angiotensin II; Angiotensin II Type 1 Receptor; Podocyte; p130Cas