Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction.
Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction.
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乙醇诱导的 Rab 蛋白改变：对垂体功能障碍的可能影响。
DOI：
10.1016/j.alcohol.2005.03.004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Emanuele,MaryAnn
中科院分区：
文献类型：
--
作者：
Ren,Jian-Ching;Zhu,Qianlong;Lapaglia,Nancy;Emanuele,NicholasV;Emanuele,MaryAnn
青春期雄性大鼠长期暴露于乙醇导致血清睾酮下降，促性腺激素、垂体促黄体激素（LH）和促卵泡激素（FSH）含量增加，血清LH和FSH水平降低或不适当正常，表明促性腺激素分泌释放受损。这种疾病背后的分子机制尚不明确，但囊泡介导的分泌过程的破坏是可能的，因为细胞内蛋白质运输途径参与糖蛋白如FSH和LH的分泌。由于Rab家族的小GTP结合蛋白被认为是哺乳动物细胞膜和蛋白运输的关键调节因子，因此本研究旨在检测乙醇损伤的垂体FSH和LH分泌是否与Rab蛋白的变化相关，特别是Rab 1B，Rab 3B，Rab 6和Rab 11。将35日龄的雄性Sprague-Dawley大鼠成对喂食含乙醇或不含乙醇的Lieber-DeCarli饮食5至60天。酒精暴露后，血清睾酮水平下降，而LH和FSH不适当的不变。免疫组织化学染色显示，乙醇处理的垂体Rab 1B，Rab 3B和Rab 11蛋白水平下降。免疫印迹显示，乙醇诱导5天后，Rab 6的短暂减少，而Rab 3B减少后20天，Rab 11后30天，Rab 1B后60天。尽管Rab蛋白发生了这些变化，但mRNA水平不受乙醇暴露的影响。我们的结论是，关键Rab蛋白的减少可能导致囊泡运输的改变，并可能在乙醇引起的垂体FSH和LH分泌中断中发挥作用。
Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) content, and decreased or inappropriately normal serum LH and FSH levels, suggesting impaired secretory release of gonadotropins. The molecular mechanisms behind this disorder are undefined, but a disruption of vesicle-mediated secretory processes is possible because intracellular protein trafficking pathways are involved in secretion of glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab family have been implicated as key regulators of membrane and protein trafficking in mammalian cells, this study was designed to test if ethanol-impaired pituitary FSH and LH secretion is associated with changes in Rab proteins, particularly Rab1B, Rab3B, Rab6, and Rab11. Male Sprague–Dawley rats 35 days old were pair-fed a Lieber–DeCarli diet with ethanol or without ethanol for 5 to 60 days. After ethanol exposure, serum testosterone levels decreased while LH and FSH were inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B, Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected by ethanol exposure. We concluded that reductions in key Rab proteins may lead to altered vesicle trafficking and may play a role in disruption of pituitary FSH and LH secretion caused by ethanol.
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DOI：
10.1111/j.1530-0277.1992.tb00677.x
发表时间：
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期刊：
Alcoholism, clinical and experimental research
影响因子：
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