Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.

摘要: Angiotensin II (AII) plays a major role in the progression of chronic kidney diseases. Podocytes are essential components ultrafiltration apparatus, and targets for AII signaling. has been shown to increase generation reactive oxygen species (ROS) podocytes. Canonical transient receptor potential-6 (TRPC6) channels stimulate Ca(2+) influx podocytes, have implicated glomerular disease. We observed that increased cationic currents rat podocytes an isolated glomerulus preparation which still attached underlying capillary. This effect was completely blocked by SKF-96365, micromolar La(3+) , siRNA knockdown TRPC6, indicating TRPC6 is primary source mobilized endogenously expressed angiotensin receptors these cells. These responses were also AT1R antagonist losartan, phospholipase C inhibitor D-609, inhibition G protein The pan-protein kinase chelerythrine had no effect. Importantly, pretreating with ROS quencher manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) eliminated activation TRPC6. Significant reductions effects on podocyte after pretreatment NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). data suggest production permits PLC-dependent cascades initiated acting AT1Rs pathway provides basis whereby two forms cellular stress-oxidative stress overload-converge common pathways relevant