As a sensor of cellular energy status, AMP-activated protein kinase (AMPK) plays an important role in the pathophysiology of diabetes and its complications. Because AMPK is also expressed in podocytes, podocyte AMPK would be an important factor contributing to development of podocyte injury. We investigated the roles of AMPK in the pathological changes of podocyte synaptopodin induced by angiotensin II (Ang II), a major injury inducer. Mouse podocytes were incubated in media containing various concentrations of Ang II and AMPK-modulating agents, and the changes of synaptopodin were analyzed by confocal imaging and Western blotting. Ang II and compound C, an AMPK inhibitor, concentrated and re-localized synaptopodin from peripheral cytoplasm to the internal cytoplasm portion in podocytes. Ang II also reduced synaptopodin protein and mRNA, which were reversed by metformin and 5-aminoimidazole-4-carboxamide ribonucleoside. Losartan, an Ang II type 1 receptor antagonist, also recovered synaptopodin mRNA, which was suppressed by Ang II. We suggest that Ang II induces the relocation and suppression of podocyte synaptopodin by suppression of AMPK and via Ang II type 1 receptor, which would be an important mechanism in Ang II-induced podocyte phenotypical changes.

The objective of this study is to investigate the direct effects of green tea catechins(GTC) on vascular smooth muscle tension and ^(46)Ca^(2+) uptake in rat aorta. The methods used in this study are isometric tension measurements using physiograph, Lanthanum method for ^(46)Cac^(2+) (2 uCi/ml) uptake measurement in rat aorta. GTC modified tension induced by 40 mM KCl or 1 uM norepinephrine in rat aorta. Low concentrations of GTC($lt;0.5 mg/m increased tension by 40 mM KCl or 1 tM norepinephrine, individually. However, high concentrations of GTC($gt; 0.5 mg/ml) inhibited tension by 40 mM KCl or 1 uM norepinephrine, individually. GTC increased ^(45)Ca uptake induced by 40 mM KCl in a dose-dependent manner. From these results, GTC has the dual actions in vascular smooth muscle in vitro. Low concentrations of GTC augments tension by K or norepinephrine. However, high concentrations of GTC inhibits tension by K or norpeinephrine. GTC may have Ca^(2+) channel activation action, which may result in unphysiological vasodilation by Ca^(2+) overload in vascular smooth muscle.