Up-regulation of ASIC3 expression by β-estradiol

Up-regulation of ASIC3 expression by β-estradiol
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β-雌二醇上调 ASIC3 表达

DOI:
10.1016/j.neulet.2018.08.012
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发表时间:
2018-09
影响因子:
2.5
通讯作者:
Wang-Ping Hu
Wang-Ping Hu
中科院分区:
医学4区
文献类型:
--
作者:
Ping Ren;Wen-Bin Wang;Hai-Hua Pan;Chun-Yu Qiu;Wang-Ping Hu

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伤害性疼痛存在性别差异,雌激素参与了性别差异。我们以前的研究表明,大鼠酸中毒引起的伤害性感受存在性别差异,雌性比雄性对乙酸更敏感。然而,性别差异背后的机制仍不清楚。我们在此报告17 β-雌二醇(E2)上调酸敏感离子通道3(ASIC 3)的表达,其可介导酸中毒诱导的事件。脂质体转染法将pCDNA3.1-ASIC 3-GFP和pCDNA3.1-ERα共转染293 T细胞。Western blot检测显示ASIC 3表达。我们发现E2以剂量和时间依赖性方式显著增加表达ASIC 3和ERα的293 T细胞中ASIC 3蛋白的表达。E2对ASIC 3蛋白表达的上调作用可被特异性ERα拮抗剂MPP完全阻断。我们还观察到大鼠背根神经节(DRG)和乙酸诱导的伤害性反应中ASIC 3的表达存在性别差异。ASIC 3蛋白在雌性大鼠DRG中的表达高于雄性大鼠DRG。雌性大鼠对醋酸引起的伤害性感受比雄性大鼠更敏感。ASIC 3蛋白在卵巢切除后DRG中的表达显著降低,但在睾丸切除后没有降低。这些结果表明,E2通过ERα上调ASIC 3的表达,这可能有助于乙酸诱导的伤害性感受的性别差异。
Sex differences occur in nociceptive pain, and estrogens are involved in the sex differences. Our previous study shows sex differences exist in acidosis-induced nociception in rats, with females being more sensitive than males to acetic acid. However, the mechanisms underlying the sex differences remain unclear. We report here17β-estradiol (E2) up-regulates expression of acid-sensing ion channel 3 (ASIC3), which can mediate the acidosis-induced events. The recombinant plasmid of pCDNA3.1-ASIC3-GFP and pCDNA3.1-estrogen receptor α (ERα) were cotransfected to 293 T cells by lipid transfection method. And western blot assays showed expression of ASIC3. We found that E2 markedly increases ASIC3 protein expression in a dose- and time- dependent manner in 293 T cells expressing ASIC3 and ERα. The up-regulating effect of E2 on ASIC3 protein expression is almost completely blocked by the addition of MPP, a specific ERα antagonist. We also observed that sex differences occur in ASIC3 expression in rat dorsal root ganglia (DRG) and in acetic acid-induced nociceptive responses. ASIC3 protein expression in female rat DRG is higher than those in male rat DRG. And female rats are more sensitive to acetic acid-induced nociception than males. ASIC3 protein expression in DRG decreases significantly after ovariectomy, but not after orchiectomy. These results suggest that E2 up-regulates ASIC3 expression through ERα, which may contribute to sex differences in acetic acid-induced nociception.
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