Sasanquasaponin up-regulates anion exchanger 3 expression and elicits cardioprotection via NO/RAS/ERK1/2 pathway
Sasanquasaponin up-regulates anion exchanger 3 expression and elicits cardioprotection via NO/RAS/ERK1/2 pathway
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茶花皂苷上调阴离子交换剂 3 表达并通过 NO/RAS/ERK1/2 通路引起心脏保护作用
DOI：
10.1139/y2012-072
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发表时间：
2012-07-01
影响因子：
2.1
通讯作者：
Huang, Min
中科院分区：
文献类型：
--
作者：
Chen, He-Ping;He, Ming;Huang, Min
我们最近发现，油茶皂苷（SQS）可以抑制缺血/再灌注诱导的细胞内Cl-浓度（[Cl-]（i））的升高，并通过上调阴离子交换器3（AE（3））的表达引起心脏保护。在本研究中，我们进一步分析了SQS上调AE（3）表达和增强心脏保护作用的细胞内信号转导途径。心肌细胞孵育24小时，与或不与10 μ mol/L SQS，随后模拟缺血/再灌注（sI/R）。适当测量NO形成、Ras活性和细胞外调节激酶1/2（ERK 1/2）磷酸化。我们发现SQS预处理有效地减弱了心肌细胞sI/R诱导的活力丧失和乳酸脱氢酶渗漏。此外，SQS还能诱导NO的产生，促进Ras的活化，进而促进细胞外调节激酶1/2（extracellularregulatedkinase 1/2，ERK 1/2）的磷酸化。这些作用被AE 3表达的增加所抵消。然而，当心肌细胞用2-（4-羧基苯基）-4，4，5，5-四甲基咪唑啉-1-氧基-3-氧化物（c-PTIO; NO清除剂）、S-反式-反式-法尼基硫代水杨酸（FTS）（Ras抑制剂），U 0126（一种ERK 1/2抑制剂），SQS预处理期间发生的AE 3表达的增加几乎完全消失，因此，SQS诱导的心脏保护作用被阻止。结果提示，SQS可能通过NO/Ras/ERK 1/2信号通路上调AE（3）表达，从而发挥心肌保护作用。
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 mu mol/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 AE3 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 AE3 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.