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Activation of IClswell by TNF-α requires CIC-3-dependent endosomal reactive oxygen production.

J Biol Chem.. 2010-07;  285(30):22864-73
James J. Matsuda, Mohammed S. Filali, Jessica G. Moreland, Francis J. Miller and Fred S. Lamb. University of Iowa, United States
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摘要

ClC-3 is a Cl-/H+ antiporter required for intra-endosomal reactive oxygen species (ROS) generation by Nox1. ClC-3 current is distinct from the swelling activated chloride current (IClswell), but over-expression of ClC-3 can activate currents that resemble IClswell. Since H2O2 activates IClswell directly, we hypothesized that ClC-3-dependent, endosomal ROS production activates IClswell. Whole-cell perforated patch clamp methods were used to record Cl- currents in cultured aortic vascular smooth muscle cells from wild-type (WT) and ClC-3 NULL mice. Under isotonic conditions TNF-α (10 ng/ml) activated outwardly rectifying Cl- currents with time-dependent inactivation in WT, but not ClC-3 NULL cells. Inhibiti... More

关键词

Chloride channels; Chloride transport; Reactive oxygen species (ROS); Thrombin; Tumor necrosis factor (TNF); chloride-proton antiporter; swelling-activated chloride channel.