Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor
Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor
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DOI：
10.1152/ajprenal.00052.2012
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发表时间：
2012-10-01
影响因子：
4.2
通讯作者：
Nonoguchi, Hiroshi
中科院分区：
文献类型：
--
作者：
Hori, Kahori;Nagai, Takanori;Nonoguchi, Hiroshi
盐皮质激素受体的核质转运需要Hori K，Nagai T，Izumi Y，Kimura M，Hasuike Y，Nakayama Y，Nanami M，Tokuyama M，Otaki Y，Kuragano T，Kohda Y，Obinata M，Kawahara K，Tanoue A，Tomita K，Nakanishi T，Nonoguchi H.Am J Physiol Renal Physiol 303：F1080-F1088,2012。2012年7月18日首次出版；DOI：10.1152/ajprenal.00052.2012。-我们之前曾报道，血管加压素V1a受体(V1aR)缺陷导致4型肾小管性酸中毒，这表明血管加压素对醛固酮的生理作用有直接影响。我们研究了加压素在植入细胞中对盐皮质激素受体(MR)核浆运输的作用。血管加压素V1aR缺陷(V1aR(-/-))小鼠肾脏髓质MR和11β-羟基类固醇脱氢酶2(11βHSD2)的表达显著降低，而氟可的松治疗可部分改善这一现象。用温度敏感型SV40大T抗原表达大鼠建立的嵌合细胞系IN-IC细胞与醛固酮或加压素孵育30min后，MR的核浆比分别从11.2%增加到47.2%和18.7%增加到61.2%，而全细胞提取液中MR的表达没有变化。免疫组织化学分析显示，与醛固酮或加压素孵育30min后，IN-IC细胞出现MRS核积聚。伴随着这些效应的是由醛固酮引起的染色体凝聚调节因子-1(RCC-1)的增加和由加压素引起的RAN GTP酶激活蛋白1(RAN Gap1)的减少。对V1aR的RNA干扰可阻断醛固酮或加压素诱导的MR核积聚。加压素增加PKCα和-β(1)的表达，而醛固酮增加PKC Delta和-Zeta的表达，但这些作用被V1aR基因敲除而取消。这些结果表明，加压素通过V1aR直接调节MRS在集合管内的核浆转运。
Hori K, Nagai T, Izumi Y, Kimura M, Hasuike Y, Nakayama Y, Nanami M, Tokuyama M, Otaki Y, Kuragano T, Kohda Y, Obinata M, Kawahara K, Tanoue A, Tomita K, Nakanishi T, Nonoguchi H. Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor. Am J Physiol Renal Physiol 303: F1080-F1088, 2012. First published July 18, 2012; doi:10.1152/ajprenal.00052.2012.-We previously reported that a deficiency in the vasopressin V1a receptor (V1aR) results in type 4 renal tubular acidosis, which suggests that vasopressin exerts direct effects on the physiological actions of aldosterone. We investigated the role of vasopressin for nucleocytoplasmic transport of mineralocorticoid receptor (MR) in the intercalated cells. Vasopressin V1aR-deficient (V1aR(-/-)) mice showed largely decreased expression of MR and 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) in the medulla of the kidney, which was partially ameliorated by fludrocortisone treatment. The incubation of IN-IC cells, an intercalated cell line established from temperature-sensitive SV40 large T antigen-expressing rats, with aldosterone or vasopressin increased the nuclear-to-cytoplasmic ratio of the MR from 11.2 to 47.2% and from 18.7 to 61.2%, respectively, in 30 min without any changes in MR expression from the whole cell extract. The immunohistochemistry analysis of the IN-IC cells revealed the nuclear accumulation of MRs after a 30-min incubation with aldosterone or vasopressin. These effects were accompanied by an increase in regulator of chromosome condensation-1 (RCC-1) due to aldosterone and a decrease in Ran GTPase-activating protein 1 (Ran Gap1) due to vasopressin. RNA interference against V1aR abolished the nuclear accumulation of MR induced by aldosterone or vasopressin. Vasopressin increased PKC alpha and -beta(1) expression, and aldosterone increased PKC delta and -zeta expression, but these effects were abolished with a V1aR knockdown. These results suggest that vasopressin directly regulates the nucleocytoplasmic transport of MRs via the V1aR in the intercalated cells of the collecting ducts.