Angiotensin II suppresses adenosine monophosphate-activated protein kinase of podocytes via angiotensin II type 1 receptor and mitogen-activated protein kinase signaling

作者：Choi Ji Young; Ha Tae Sun^*; Park Hye Young; Ahn Hee Yul

来源：Clinical and Experimental Nephrology, 2013, 17(1): 16-23.

DOI：10.1007/s10157-012-0649-8

• AMP-activated protein kinase
• Angiotensin II
• Podocyte
• Angiotensin II type 1 receptor
• MAPK

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. %26lt;br%26gt;Mouse podocytes were incubated in media containing various concentrations of Ang II and AMPK-modulating agents. The changes of AMPK alpha were analyzed by confocal imaging and Western blotting in response to Ang II. %26lt;br%26gt;Ang II changed the localization of AMPK alpha from peripheral cytoplasm into internal cytoplasm and peri- and intranuclear areas in podocytes. Ang II also reduced AMPK alpha (Thr172) phosphorylation in time- and dose-sensitive manners. In particular, 10(-7) M Ang II reduced phospho-AMPK alpha significantly and continuously at 6, 24, and 48 h. AMPK activators, metformin and 5-aminoimidazole-4-carboxamide-1 beta-riboside, restored the suppressed AMPK alpha (Thr172) phosphorylation. Losartan, an Ang II type 1 receptor antagonist, also recovered the suppression and the mal-localization of AMPK alpha, which were induced by Ang II. PD98059, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor, also restored the AMPK alpha (Thr172) phosphorylation suppressed by Ang II. %26lt;br%26gt;We suggest that Ang II induces the relocation and suppression of podocyte AMPK alpha via Ang II type 1 receptor and MAPK signaling pathway, which would be an important mechanism in Ang II-induced podocyte injury.

• 出版日期2013-2