Anzeige
Erschienen in:
01.02.2013 | Original Article
Angiotensin II suppresses adenosine monophosphate-activated protein kinase of podocytes via angiotensin II type 1 receptor and mitogen-activated protein kinase signaling
Erschienen in: Clinical and Experimental Nephrology | Ausgabe 1/2013
Einloggen, um Zugang zu erhaltenAbstract
Background
Adenosine monophosphate (AMP)-activated protein kinase (AMPK), as a sensor of cellular energy status, has been known to play an important role in the pathophysiology of diabetes and its complications. As AMPK is also expressed in podocytes, it is possible that podocyte AMPK would be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPK in the pathological changes of podocytes induced by angiotensin II (Ang II), a major injury inducer in diabetic proteinuria.
Methods
Mouse podocytes were incubated in media containing various concentrations of Ang II and AMPK-modulating agents. The changes of AMPKα were analyzed by confocal imaging and Western blotting in response to Ang II.
Results
Ang II changed the localization of AMPKα from peripheral cytoplasm into internal cytoplasm and peri- and intranuclear areas in podocytes. Ang II also reduced AMPKα (Thr172) phosphorylation in time- and dose-sensitive manners. In particular, 10−7 M Ang II reduced phospho-AMPKα significantly and continuously at 6, 24, and 48 h. AMPK activators, metformin and 5-aminoimidazole-4-carboxamide-1β-riboside, restored the suppressed AMPKα (Thr172) phosphorylation. Losartan, an Ang II type 1 receptor antagonist, also recovered the suppression and the mal-localization of AMPKα, which were induced by Ang II. PD98059, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor, also restored the AMPKα (Thr172) phosphorylation suppressed by Ang II.
Conclusion
We suggest that Ang II induces the relocation and suppression of podocyte AMPKα via Ang II type 1 receptor and MAPK signaling pathway, which would be an important mechanism in Ang II-induced podocyte injury.