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通过蛋白质组学分析发现,大鼠大脑中与应激暴露相关的海马胆碱能神经刺激肽前体蛋白减少。

Decreased hippocampal cholinergic neurostimulating peptide precursor protein associated with stress exposure in rat brain by proteomic analysis.

作者信息

Kim Hong Gi, Kim Kil Lyong

机构信息

Biochemistry Laboratory, Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.

出版信息

J Neurosci Res. 2007 Oct;85(13):2898-908. doi: 10.1002/jnr.21407.

Abstract

The stress response alters behavior, autonomic function, and secretion of multiple hormones, including corticotropin-releasing factor, adrenocorticotropin hormone, and cortisol, through the hypothalamic-pituitary-adrenal axis. Constitutive stress responses lead to a number of psychiatric disorders, including depression, posttraumatic stress disorder, Alzheimer's disease (AD), and other anxiety disorders through increased stress hormones and other unknown factors. Here, we performed a proteomic analysis of rat brain exposed to restraint stress compared with a nonstress group by using 2D-DIGE and MALDI-TOF analysis. Several proteins were identified by peptide mass fingerprint (PMF), including down-regulated hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp). The current study demonstrates that HCNP-pp mRNA and protein expression are decreased in rat hippocampus after stress exposure. The level of HCNP-pp in H19-7, a rat hippocampal cell line, significantly decreases with dexamethasone treatment, a synthetic glucocorticoid. Thus, this finding suggests that HCNP-pp expression may decrease in response to stress exposure. Decreased HCNP-pp from stress exposure may result in lower levels of HCNP that might contribute to a loss of acetylcholine production.

摘要

应激反应通过下丘脑 - 垂体 - 肾上腺轴改变行为、自主神经功能以及多种激素的分泌,这些激素包括促肾上腺皮质激素释放因子、促肾上腺皮质激素和皮质醇。持续性应激反应会通过应激激素增加和其他未知因素导致多种精神疾病,包括抑郁症、创伤后应激障碍、阿尔茨海默病(AD)以及其他焦虑症。在此,我们通过二维差异凝胶电泳(2D - DIGE)和基质辅助激光解吸电离飞行时间质谱(MALDI - TOF)分析,对暴露于束缚应激的大鼠大脑与非应激组进行了蛋白质组学分析。通过肽质量指纹图谱(PMF)鉴定出了几种蛋白质,其中包括下调的海马胆碱能神经刺激肽前体蛋白(HCNP - pp)。当前研究表明,应激暴露后大鼠海马中HCNP - pp的mRNA和蛋白质表达均降低。在大鼠海马细胞系H19 - 7中,HCNP - pp的水平随着合成糖皮质激素地塞米松的处理而显著降低。因此,这一发现表明HCNP - pp的表达可能会因应激暴露而降低。应激暴露导致的HCNP - pp减少可能会导致HCNP水平降低,这可能会导致乙酰胆碱生成减少。

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