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Anion exchanger 3 is required for sasanquasaponin to inhibit ischemia/reperfusion-induced elevation of intracellular Cl- concentration and to elicit cardioprotection.

Abstract
Recent studies have shown that the cardioprotection of sasanquasaponin (SQS) against ischemia/reperfusion injury is related to inhibiting ischemia/reperfusion-induced elevation of intracellular Cl(-) concentration ([Cl(-) ](i)). However, the mechanism of inhibition remains unclear. Anion exchanger 3 (AE(3)) is an important regulatory protein for [Cl(-)](i). This study investigated whether AE(3) plays the critical role in the inhibitory effect of SQS on elevation of [Cl(-)](i) induced by ischemia/reperfusion and mediates the cardioprotection of SQS in H9c2 cells. Normal and AE(3) -knockdown H9c2 cells were incubated for 24 h with or without various concentrations of SQS (0.1, 1, or 10 µM) followed by simulated ischemia/reperfusion (sI/R). AE(3) expression was detected by Western blot. Flow cytometer analysis was employed to determine [Cl(-)](i,) [Ca(2+)](i) , reactive oxygen species (ROS) production, and cell apoptosis. The results showed that SQS pretreatment concentration-dependently attenuated sI/R-induced viability loss and lactate dehydrogenase leakage in normal H9c2 cells. Additionally, SQS concentration-dependently up-regulated AE(3) protein expression, and inhibited sI/R-induced the elevation of [Cl(-)](i) followed by the attenuation of Ca(2+) overload, ROS production, and cell apoptosis. However, the dose-dependent cardioprotection induced by SQS was abolished in AE(3) -knockdown H9c2 cells, and the inhibitory effects of SQS on [Cl(-)](i), Ca(2+) overload, ROS production, and cell apoptosis were also reversed. Our data indicate that AE(3) mediates the cardioprotective effect of SQS against sI/R injury. Importantly, AE(3) is required for SQS to inhibit sI/R-induced elevation of [Cl(-)](i), which subsequently inhibited sI/R-induced Ca(2+) overload, ROS production, and cell apoptosis.
AuthorsHe-Ping Chen, Ming He, Zhu-Jun Mei, Qi-Ren Huang, Weijie Peng, Min Huang
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 112 Issue 10 Pg. 2803-12 (Oct 2011) ISSN: 1097-4644 [Electronic] United States
PMID21608017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Wiley-Liss, Inc.
Chemical References
  • 22-O-angeloylcamelliagenin C-3-O-(glucopyranosyl-1-2)(glucopyranosyl-1-2-O-arabinopyranosyl-1-3-)glucopyranosiduronic acid
  • Antiporters
  • Chlorides
  • Reactive Oxygen Species
  • Saponins
  • Slc4a3 protein, rat
  • Calcium
Topics
  • Antiporters (genetics, metabolism)
  • Apoptosis (drug effects)
  • Blotting, Western
  • Calcium (metabolism)
  • Cell Survival (drug effects)
  • Chlorides (metabolism)
  • Flow Cytometry
  • Myocardial Reperfusion Injury (physiopathology)
  • Reactive Oxygen Species (metabolism)
  • Saponins (pharmacology)

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