Sasanquasaponin up-regulates anion exchanger 3 expression and elicits cardioprotection via NO/RAS/ERK1/2 pathway.

We have shown recently that sasanquasaponin (SQS) can inhibit ischemia/reperfusion-induced elevation of intracellular Cl(-) concentration ([Cl(-)](i)) and elicit cardioprotection by up-regulating anion exchanger 3 (AE(3)) expression. In the present study, we futher analysed the intracellular signal transduction pathways by which SQS up-regulates AE(3) expression and elicits cardioprotection. Cardiomyocytes were incubated for 24 h with or without 10 µmol/L SQS, followed by simulated ischemia/reperfusion (sI/R). NO formation, Ras activity, and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation were measured appropriately. We showed that SQS pretreatment efficiently attenuated viability loss and lactate dehydrogenase leakage induced by sI/R in cardiomyocytes. Moreover, SQS induced NO production and promoted Ras activation, which futher promoted extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation. These effects were paralleled by an increase in AE(3) expression. However, when the cardiomyocytes were treated with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide (c-PTIO; an NO scavenger), S-trans-trans-farnesylthiosalicylic acid (FTS) (a Ras inhibitor), U0126 (an ERK1/2 inhibitor), respectively, the increase in AE(3) expression occurring during SQS pretreatment was almost completely abolished and, as a result, SQS-induced cardioprotection was prevented. Our findings indicate that SQS might up-regulate AE(3) expression through NO/Ras/ERK1/2 signal pathway to elicit cardioprotection in cultured cardiomyocytes.
AuthorsHe-Ping Chen, Ming He, Zhu-Jun Mei, Qi-Ren Huang, Min Huang
JournalCanadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 90 Issue 7 Pg. 873-80 (Jul 2012) ISSN: 1205-7541 [Electronic] Canada
PMID22693949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 22-O-angeloylcamelliagenin C-3-O-(glucopyranosyl-1-2)(glucopyranosyl-1-2-O-arabinopyranosyl-1-3-)glucopyranosiduronic acid
  • Antiporters
  • Cardiotonic Agents
  • Saponins
  • Slc4a3 protein, rat
  • Nitric Oxide
  • L-Lactate Dehydrogenase
  • ras Proteins
  • Animals
  • Antiporters (metabolism)
  • Cardiotonic Agents (pharmacology)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • L-Lactate Dehydrogenase (metabolism)
  • MAP Kinase Signaling System (drug effects)
  • Myocardial Reperfusion Injury (drug therapy, metabolism)
  • Myocytes, Cardiac (drug effects, metabolism)
  • Nitric Oxide (metabolism)
  • Phosphorylation (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (drug therapy, metabolism)
  • Saponins (pharmacology)
  • Signal Transduction (drug effects)
  • Up-Regulation (drug effects)
  • ras Proteins (metabolism)

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