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首页> 外文期刊>Endocrinology >Activating Transcription Factor 6 alpha Is Required for the Vasopressin Neuron System to Maintain Water Balance Under Dehydration in Male Mice
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Activating Transcription Factor 6 alpha Is Required for the Vasopressin Neuron System to Maintain Water Balance Under Dehydration in Male Mice

机译:加压素神经元系统需要激活转录因子6 alpha来维持雄性小鼠脱水下的水分平衡

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Activating transcription factor 6 alpha (ATF6 alpha) is a sensor of endoplasmic reticulum (ER) stress and increases the expression of ER chaperones and molecules related to the ER-associated degradation of unfolded/misfolded proteins. In this study, we used ATF6 alpha knockout (ATF6 alpha(-/-)) mice to clarify the role of ATF6 alpha in the arginine vasopressin (AVP) neuron system. Although urine volumes were not different between ATF6 alpha(-/-) and wild-type (ATF6 alpha(-/-)) mice with access to water ad libitum, they were increased in ATF6 alpha(-/-) mice compared with those in ATF6 alpha(-/-) mice under intermittent water deprivation (WD) and accompanied by less urine AVP in ATF6 alpha(-/-) mice. The mRNA expression of immunoglobulin heavy chain binding protein, an ER chaperone, was significantly increased in the supraoptic nucleus in ATF6 alpha(-/-) but not ATF6 alpha(-/-) mice after WD. Electron microscopic analyses demonstrated that the ER lumen of AVP neurons was more dilated in ATF6 alpha(-/-) mice than in ATF6 alpha(-/-) mice after WD. ATF6 alpha(-/-) mice that were mated with mice possessing a mutation causing familial neurohypophysial diabetes insipidus (FNDI), which is characterized by progressive polyuria and AVP neuronal loss due to the accumulation of mutant AVP precursor in the ER, manifested increased urine volume under intermittent WD. The aggregate formation in the ER of AVP neurons was further impaired in FNDI/ATF6 alpha(-/-) mice compared with that in FNDI mice, and AVP neuronal loss was accelerated in FNDI/ATF6 alpha(-/-) mice under WD. These data suggest that ATF6 alpha is required for the AVP neuron system to maintain water balance under dehydration.
机译:激活转录因子6 alpha(ATF6 alpha)是内质网(ER)压力的传感器,可增加ER伴侣和与ER相关折叠的/折叠错误的蛋白质降解相关的分子的表达。在这项研究中,我们使用了ATF6 alpha基因敲除(ATF6 alpha(-/-))小鼠来阐明ATF6 alpha在精氨酸加压素(AVP)神经元系统中的作用。尽管ATF6 alpha(-/-)和随意取水的野生型(ATF6 alpha(-/-))小鼠的尿量没有差异,但与那些相比,ATF6 alpha(-/-)小鼠的尿量增加了在间歇性缺水(WD)下的ATF6 alpha(-/-)小鼠体内,并伴有较少的ATF6 alpha(-/-)小鼠尿液AVP。 WD后,ATF6 alpha(-/-)小鼠的视上核中免疫球蛋白重链结合蛋白(一种ER伴侣)的mRNA表达显着增加。电子显微镜分析表明,WD后,ATF6 alpha(-/-)小鼠中AVP神经元的ER内腔比在ATF6 alpha(-/-)小鼠中的扩张更大。与具有导致家族性神经下垂体尿崩症(FNDI)的突变的小鼠交配的ATF6 alpha(-/-)小鼠,其特征是由于突变AVP前体在ER中的积累而导致进行性多尿和AVP神经元丢失,表现为尿液增加间歇WD下的音量。与FNDI小鼠相比,FNDI / ATF6 alpha(-/-)小鼠的AVP神经元内质网的聚集形成进一步受到损害,而WD下FNDI / ATF6 alpha(-/-)小鼠中AVP神经元的损失加速。这些数据表明AVP神经元系统需要ATF6 alpha才能在脱水下维持水平衡。

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