Abstract |
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.
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Authors | He-Ping Chen, Ming He, Zhu-Jun Mei, Qi-Ren Huang, Min Huang |
Journal | Canadian journal of physiology and pharmacology
(Can J Physiol Pharmacol)
Vol. 90
Issue 7
Pg. 873-80
(Jul 2012)
ISSN: 1205-7541 [Electronic] Canada |
PMID | 22693949
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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Topics |
- 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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