| 1 | Neurochem. Res. 2004 Jun 29: 1245-55 |
|---|---|
| PMID | 15176481 |
| 标题 | 在精神分裂症中，前额叶皮质中代谢酶和蛋白酶抑制剂的基因表达降低。 |
| Abstract | 微阵列表达研究报道了组氨酸三合会核苷酸结合蛋白的mRNA表达降低（Hint1) and cytosolic malate dehydrogenase (MDH1) in the dorsolateral prefrontal cortex (DLPFC) of individuals withschizophrenia。Microarray results for neuroserpin (SERPINI1) mRNA in the DLPFC have reported increased and decreased expression in individuals withschizophrenia。相对丰度Hint1DLPFC中的人，MDH1和SERPINI1 mRNAschizophreniaand controls were measured by real-time quantitative polymerase chain reaction (Q-PCR) and forHint1expression by in situ hybridization. The Q-PCR results were compared by analysis of covariance between individuals withschizophrenia和控件。基因表达水平Hint1两组之间，，MDH1和SERPINI1显着差异。男性schizophreniacompared to male controls showed reductions by 2.8- to 3.7-fold ofHint1, neuroserpin, and MDH1 by Q-PCR. The decreases in mRNA abundance for MDH1 (P = 0.006),Hint1（p = 0.050）和雄性个体DLPFC中的神经素（p = 0.005）schizophrenia与先前的报告一致。Hint1在VI层中将mRNA显着降低了34％。尽管与性别没有显着相互作用，但女性患者与女性对照组之间的基因表达没有差异。这些结果证实了较早的报告，并提出了与DLPFC中代谢和蛋白酶活性相关的特定基因的异常，可能被认为是男性患者的分子途径的一部分schizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | 神经心理药理学2007年8月32日：1774-82 |
| PMID | 17203012 |
| 标题 | Supersensitivity to amphetamine in protein kinase-C interacting protein/HINT1 knockout mice. |
| Abstract | 蛋白激酶C相互作用蛋白/组氨酸三合会核苷酸结合蛋白1（PKCI/Hint1)是一种蛋白质famil组氨酸三合会的成员y. Although this protein is widely expressed in the mammalian brain including mesocorticolimbic and mesostriatal regions, its physiological function in CNS remains unknown. Recent microarray studies reported decreased mRNA expression of PKCI/Hint1在个人的额叶皮层中schizophrenia, suggesting the possible involvement of this protein in the pathophysiology of the disease. In view of the documented link between dopamine (DA) transmission andschizophrenia, the present study used behavioral and neurochemical approaches to examine the influence of constitutive PKCI/Hint1删除：（i）基底和苯丙胺（AMPH）诱发的运动活性；（ii）背纹状体中的DA动力学和（iii）突触后DA受体功能。pkci/Hint1(-/-) (KO) mice displayed lower spontaneous locomotion relative to wild-type (WT) controls. Acute AMPH administration significantly increased locomotor activity in WT mice; nonetheless, the effect was enhanced in KO mice. Quantitative microdialysis studies revealed no alteration in basal DA dynamics in the striatum or nucleus accumbens of KO mice. The ability of acute AMPH to increase DA levels was unaltered indicating that function in presynaptic DA neurotransmission in these regions do not underlie the behavioral phenotype of KO mice. In contrast to WT mice, systemic administration of the direct-acting DA receptor agonist apomorphine (10 mg/kg) significantly increased locomotor activity in KO mice suggesting that postsynaptic DA function is altered in these animals. These results demonstrate an important role of PKCI/Hint1in modulating the behavioral response to AMPH. Furthermore, they indicate that the absence of this protein may be associated with dysregulation of postsynaptic DA transmission. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Schizophr. Res. 2008 Dec 106: 200-7 |
| PMID | 18799291 |
| 标题 | 组氨酸三合会核苷酸结合蛋白1（HINT1）是否是精神分裂症的候选者？ |
| Abstract | : The histidine triad nucleotide-binding protein 1,Hint1，水解腺苷5'单磷酰胺层底物，例如Amp-Morpholiders。人类Hint1gene is located on chromosome 5q31.2, a region implicated in linkage studies ofschizophrenia。Hint1已证明在验尸大脑之间表达不同的表达schizophrenia患者和不受影响的对照。还发现它与突触后多巴胺传播的失调有关，因此表明在几种神经精神疾病中具有潜在的作用。 : In this work, we studied 8 SNPs around theHint1使用爱尔兰高密度研究的基因区域schizophreniafamilies (ISHDSF, 1350 subjects and 273 pedigrees) and the Irish case control study ofschizophrenia（ICCSS，655名受试者和626个对照）。表达式Hint1比较了来自schizophrenicpatients and unaffected controls provided by the Stanley Medical Research Institute. ：我们发现，在性分层的分析中，ISHDSF和ICCS样本的几个SNP中的等位基因频率具有显着差异。但是，两个样本之间的性别效应有所不同。在表达研究中，患者和对照组之间没有观察到表达的显着差异。然而，观察到性别，诊断和RS3864283基因型之间的显着相互作用。 ：来自关联和表达研究的数据表明，在Hint1可能与schizophrenia协会可能是特定于性别的。然而，显示关联的标记与先前在同一样品中报道的SPEC2/PDZ-GEF2/ACSL6基因座高LD。这使得很难在这些基因之间分离关联信号。其他独立研究可能需要区分这些候选基因。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Schizophr. Res. 2008 Dec 106: 200-7 |
| PMID | 18799291 |
| 标题 | 组氨酸三合会核苷酸结合蛋白1（HINT1）是否是精神分裂症的候选者？ |
| Abstract | : The histidine triad nucleotide-binding protein 1,Hint1，水解腺苷5'单磷酰胺层底物，例如Amp-Morpholiders。人类Hint1gene is located on chromosome 5q31.2, a region implicated in linkage studies ofschizophrenia。Hint1已证明在验尸大脑之间表达不同的表达schizophrenia患者和不受影响的对照。还发现它与突触后多巴胺传播的失调有关，因此表明在几种神经精神疾病中具有潜在的作用。 : In this work, we studied 8 SNPs around theHint1使用爱尔兰高密度研究的基因区域schizophreniafamilies (ISHDSF, 1350 subjects and 273 pedigrees) and the Irish case control study ofschizophrenia（ICCSS，655名受试者和626个对照）。表达式Hint1比较了来自schizophrenicpatients and unaffected controls provided by the Stanley Medical Research Institute. ：我们发现，在性分层的分析中，ISHDSF和ICCS样本的几个SNP中的等位基因频率具有显着差异。但是，两个样本之间的性别效应有所不同。在表达研究中，患者和对照组之间没有观察到表达的显着差异。然而，观察到性别，诊断和RS3864283基因型之间的显着相互作用。 ：来自关联和表达研究的数据表明，在Hint1可能与schizophrenia协会可能是特定于性别的。然而，显示关联的标记与先前在同一样品中报道的SPEC2/PDZ-GEF2/ACSL6基因座高LD。这使得很难在这些基因之间分离关联信号。其他独立研究可能需要区分这些候选基因。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Neuropsychopharmacology 2009 Jan 34: 18-54 |
| PMID | 18923405 |
| 标题 | Target identification for CNS diseases by transcriptional profiling. |
| Abstract | 基因表达在神经精神病学和神经退行性疾病中的变化以及对治疗药物的基因反应，提供了鉴定中枢神经系统（CNS）药物发现靶标的新方法。这篇综述总结了基因和途径的靶向在人类后脑，动物模型和细胞培养研究的表达分析中所复制的。分析人类神经元的分析暗示了阿尔茨海默氏病的靶标，以及与正常衰老和轻度认知障碍有关的认知下降。除TAU，淀粉样蛋白β前体蛋白和淀粉样蛋白β肽（ABETA）外，这些靶标还包括所有三种高亲和力神经营养蛋白受体以及成纤维细胞生长因子（FGF）系统，突触标记，谷氨酸受体（GLURS）和转运者（GLURS）和转运者（GLURS）和转运者和多巴胺（DA）受体，尤其是D2亚型。基于基因的帕金森氏病（PD）的候选者包括泛素 - 蛋白酶系统，反应性氧的清除剂，脑衍生的神经营养因子（BDNF），其受体，TRKB和下游靶标早期生长反应1，NURR-1和NURR-1和NURR-1和NURR-1，和NURR-1，和NURR-1，和NURR-1，和NURR-1和通过蛋白激酶C和RAS途径传导。从中年到老年，大脑mRNA产生的变异性增加和降低表明，正常衰老期间的认知障碍可以通过恢复抗氧化剂，DNA修复和突触功能（包括DA到年轻人水平）的药物来解决。研究schizophreniaidentify robust decreases in genes for GABA function, including glutamic acid decarboxylase,Hint1，谷氨酸转运和毛刺，BDNF和TRKB，许多14-3-3蛋白家族成员，以及中枢神经系统突触和代谢功能的基因降低，尤其是糖酵解和ATP的生成。这些代谢基因中的许多因胰岛素和毒蕈碱激动剂而增加，它们在精神病中均具有治疗性。差异基因组信号在躁郁症中相对稀疏，但包括14-3-3蛋白构件的表达中的缺陷，这意味着这些伴侣蛋白和神经递质途径是它们支持的药物靶标。患有重度抑郁症患者的大脑显示，谷氨酸转运和代谢，神经营养信号传导（例如FGF，BDNF和VGF）以及MAP激酶途径的基因表达降低。暴露于电击性休克的动物的大脑中，这些途径的增加和抗抑郁治疗鉴定了神经营养性和血管生长生长因子和第二信使刺激作为治疗抑郁症的治疗方法。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | BMC Neurosci 2009 -1 10: 132 |
| PMID | 19912621 |
| 标题 | 与血浆皮质酮水平升高有关的PKCI/HINT1基因敲除小鼠中的抗抑郁药和抗焦虑行为。 |
| Abstract | Protein kinase C interacting protein (PKCI/Hint1）是一种属于组氨酸三合会（HIT）家族蛋白的小蛋白质。它的大脑免疫反应性位于神经元和神经元过程中。pkci/Hint1gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom ofschizophrenia在动物模型中。验尸研究确定了PKCI/Hint1作为候选分子schizophreniaand bipolar disorder. We investigated the hypothesis that the PKCI/Hint1gene may play an important role in regulating mood function in the CNS. We submitted PKCI/Hint1KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/Hint1KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/Hint1KO mice was significantly higher than in the WT. pkci/Hint1KO小鼠表现出行为和内分泌特征的表型，表明情绪功能的变化，包括抗焦虑样和抗抑郁药，如行为，以及血浆中皮质酮水平升高。这些结果表明，PKCI/提示1基因对于中枢神经系统中的情绪调节功能可能很重要。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | PLoS ONE 2011 -1 6: e20589 |
| PMID | 21655227 |
| 标题 | 通过使用DNA微阵列分析，通过纯合性映射来鉴定新的精神分裂症基因座。 |
| Abstract | 高分辨率DNA微阵列的最新发展，其中成千上万的单核苷酸多态性（SNP）是基因型的，可以快速鉴定出复杂疾病的易感基因。这些SNP的簇可能显示出可以分析与疾病关联的纯合性（ROHS）。对父母是堂兄的患者的分析使他们可以在其后代中寻找自身的段。在这里，使用Affymetrix actemetrix actomemetrix actomemetrix actem acter snp阵列5.0确定ROHS，我们为9个个体进行了基因分型schizophrenia（SCZ）父母是第一个堂兄。我们在染色体1、3、4、6、7、8、9、10、11、12、12、13、16、17、19、20和21的染色体上确定了重叠的ROH。先前仅报道了5号染色体上的基因座。5q23.3-Q31.1染色体上的ROHS包括候选基因组氨酸三合会核苷酸结合蛋白1（Hint1）和酰基-COA合成酶长链家族成员6（ACSL6）。考虑到SCZ的高度杂合性，其他重叠的ROH可能包含新型的稀有隐性变体，这些变体在我们的样品中特别影响SCZ。对父母是堂兄的患者的分析可能会为精神病的遗传分析提供新的见解。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Pharmacogenomics J. 2011 Aug 11: 251-7 |
| PMID | 20514075 |
| 标题 | 组氨酸三合一核苷酸结合蛋白-1（HINT1）基因变体与尼古丁依赖性的关联。 |
| Abstract | 组氨酸三合会核苷酸结合蛋白1基因（Hint1) is implicated inschizophreniaand in the behavioral effects of morphine and amphetamine. Because nicotine dependence (ND) is highly comorbid withschizophreniaand other substance abuse, we examined the association ofHint1与nd。来自两个独立样本的协会分析表明Hint1基因变异与ND表型相关。此外，人类验尸mRNA表达表明吸烟状态和基因型影响Hint1在大脑中的表达。在动物研究中，蛋白质印迹分析显示Hint1protein level in the mouse nucleus accumbens (NAc) after chronic nicotine exposure. This increase was reduced after treatment with the nicotinic-receptor antagonist mecamylamine, and 24 and 72?h after cessation of nicotine treatment. These results indicate a genetic association betweenHint1变体和nd，并表明尼古丁诱导的调制Hint1level may be involved in mechanisms of excess smoking. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Eur Arch Psychiatry Clin Neurosci 2012 Mar 262: 167-72 |
| PMID | 21553311 |
| 标题 | Differential expression of HINT1 in schizophrenia brain tissue. |
| Abstract | 文献中的最新发现表明，组氨酸三合会核苷酸结合蛋白1（Hint1）和精神疾病，例如严重抑郁症，焦虑和schizophrenia, although its physiological roles are not completely comprehended. Using Western blot, we comparedHint1protein expression in the postmortem dorsolateral prefrontal cortex and thalamus ofschizophrenia患者和健康对照，有助于阐明Hint1inschizophreniapathophysiology.Hint1was found to be downregulated in the dorsolateral prefrontal cortex and upregulated in the thalamus. Our results combined to previous studies in human samples and preclinical models support the notion thatHint1must be more explored as a potential target for psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Transl Psychiatry 2012 -1 2: e87 |
| PMID | 22832852 |
| 标题 | Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients. |
| Abstract | 重度抑郁症（MDD）是全球残疾的主要原因，每年西方社会丧生近一百万生命。这是由于对疾病病理生理学的了解不足以及缺乏准确诊断或指导抗抑郁治疗策略的经验医学测试。在这里，我们在分析24例MDD患者和12个匹配对照的验尸后外侧前额叶皮层脑组织中使用了shot弹枪蛋白质组学。通过凝胶电泳预先分级，并通过shot弹枪独立的无标签液相色谱 - 质谱法对脑蛋白质组进行了预分级。这导致了MDD和控制受试者之间不同蛋白质组指纹的鉴定。这些差异中的一些通过蛋白质印迹或选定的反应监测质谱法验证。这包括与能量代谢和突触功能相关的蛋白质，我们还发现组氨酸三合会核苷酸结合蛋白1（Hint1），最近与情绪和行为的调节有关。我们还发现（n = 11）和没有（n = 12）精神病的MDD中的差异蛋白质组谱。有趣的是，精神病指纹显示出与大脑蛋白质组发生变化的明显重叠schizophrenia患者。这些发现表明，可以通过基于不同脑蛋白质组学特征区分MDD的不同亚型来为疾病理解做出贡献。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Genes Brain Behav. 2012 Nov 11: 993-1000 |
| PMID | 22827509 |
| 标题 | Acute behavioral effects of nicotine in male and female HINT1 knockout mice. |
| Abstract | 人类遗传关联和脑表达研究以及小鼠的行为和分子研究暗示了组氨酸三合会核苷酸结合蛋白的作用1（Hint1） 在schizophrenia，躁郁症，抑郁和焦虑。吸烟和精神疾病之间的合并症很高，schizophreniain particular, is well established. Associations withschizophreniaandHint1也是性别的，在男性中的影响更大。但是，尚不清楚与基因相关的性别差异是否扩展到其他表型。因此，在这项研究中，使用一系列行为测试，我们阐明了Hint1在使用男性和女性的急性尼古丁介导的行为中Hint1野生型（+/+）和敲除（ - / - ）小鼠。结果表明男性Hint1- / - 小鼠对尾flick的急性尼古丁诱导的抗伤害感受的敏感性不太敏感，但没有热板测试。低尼古丁剂量，男性和女性Hint1- / - 小鼠对尼古丁诱导的低动力的敏感性较小，尽管这种作用在女性中更为明显。在男性中观察到的运动活性的基线差异Hint1+/+ and -/- mice were absent in females. Nicotine did not produce an anxiolytic effect in maleHint1-/- mice, but rather an anxiogenic response. Diazepam also failed to induce an anxiolytic response in these mice, suggesting a general anxiety phenotype not specific to nicotine. Differences in anxiety-like behavior were not observed in female mice. These results further support a role forHint1在尼古丁介导的行为中，表明基因的改变可能对男性和女性的表型具有不同的影响。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Mol Brain 2013 -1 6：42 |
| PMID | 24093505 |
| 标题 | Hint1protein cooperates with cannabinoid 1 receptor to negatively regulate glutamate NMDA receptor activity. |
| Abstract | G protein-coupled受体(GPCRs)目标s of a large number of drugs currently in therapeutic use. Likewise, the glutamate ionotropic N-methyl-D-aspartate receptor (NMDAR) has been implicated in certain neurological disorders, such as neurodegeration, neuropathic pain and mood disorders, as well as psychosis andschizophrenia。因此，现在有一个重要的需求来表征GPCR和NMDAR之间的相互作用。实际上，这些相互作用会产生独特的作用，而Mu-Apioid受体（MOR）的激活增加了与NMDAR相关的钙通量，而1型1型大麻素受体（CNR1）的钙会拮抗它们的渗透。值得注意的是，一系列蛋白质与这些受体相互作用，影响其反应和相互作用，然后成为上述病理学的新型治疗靶标。 我们发现在GPCR存在的情况下Hint1protein influences the activity of NMDARs, whereby NMDAR activation was enhanced in CNR1+/+/Hint1-/- cortical neurons and the cannabinoid agonist WIN55,212-2 provided these cells with no protection against a NMDA insult. NMDAR activity was normalized in these cells by the lentiviral expression ofHint1, which also restored the neuroprotection mediated by cannabinoids. NMDAR activity was also enhanced in CNR1-/-/Hint1+/+神经元，尽管该活性被MOR，CNR1或5-羟色胺1A（5HT1AR）等GPCR的表达抑制。 这Hint1protein plays an essential role in the GPCR-NMDAR connection. In the absence of receptor activation, GPCRs collaborate withHint1proteins to negatively control NMDAR activity. When activated, most GPCRs release the control ofHint1and NMDAR responsiveness is enhanced. However, cannabinoids that act through CNR1 maintain the negative control ofHint1关于NMDAR功能及其对谷氨酸兴奋性毒性侮辱的保护。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Neurosci. Lett. 2013 Aug 550: 129-33 |
| PMID | 23810802 |
| 标题 | 组氨酸三合会核苷酸结合1蛋白参与小鼠尼古丁奖励和物理尼古丁的戒断。 |
| Abstract | Smoking rates among individuals withschizophreniaare significantly higher than the general population. One possible explanation for this comorbidity is that there are shared genes and biological pathways between smoking andschizophrenia。这histidine triad nucleotide binding protein 1 (Hint1）是一个潜在的候选者，因为遗传关联和表达研究暗示了这两个基因schizophreniaand nicotine dependence; however, the behavioral role ofHint1in nicotine dependence is unknown. Thus, the goal of the current study was to determine the behavioral role ofHint1in nicotine dependence. We tested maleHint1wild-type (+/+) and knockout (-/-) mice in the nicotine conditioned place preference (CPP) test of reward, a nicotine withdrawal model assessing both physical and affective signs, and the nicotine withdrawal conditioned place aversion (CPA) test.Hint1-/- mice failed to develop a significant nicotine CPP and physical withdrawal signs (hyperalgesia and somatic signs) were attenuated inHint1-/- mice. Conversely,Hint1-/- mice developed a significant nicotine withdrawal CPA similar to their ++ counterparts. Overall, our data support a role for theHint1与尼古丁奖励和身体戒断相关的介导行为中的基因，并洞悉Hint1in nicotine dependence-like behaviors. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Zhongguo yi Xue ke Xue Yuan Xue Bao 2014 8月36日：454-60 |
| PMID | 25176218 |
| 标题 | [Histidine triad nucleotide-binding protein 1 and human diseases]. |
| Abstract | Histidine triad nucleotide-binding protein 1 (Hint1) is a member of a superfamily of histidine triad proteins named by the conserved nucleotide-binding motif histidine-x-histidine-x-histidine-xx, in which x represents hydrophobic amino acid.Hint1与许多人类疾病的病理进步有关，包括癌症和schizophrenia; however, little is known about the essential role and pathological consequences ofHint1in cellular physiology and diseases. Therefore, we summarize the structure, distribution, and physiological function ofHint1在细胞和组织中以及之间的相关性Hint1和人类疾病。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Front Pharmacol 2014 -1 4：169 |
| PMID | 24427139 |
| 标题 | 这cannabinoid receptor 1 associates with NMDA receptors to produce glutamatergic hypofunction: implications in psychosis and schizophrenia. |
| Abstract | 神经系统throughou非常普遍t the central nervous system and its type 1 receptor (CB1) plays a crucial role in preventing the neurotoxicity caused by activation of glutamate N-methyl-D-aspartate receptors (NMDARs). Indeed, it is the activity of NMDARs themselves that provides the demands on the endogenous cannabinoids in order to control their calcium currents. Therefore, a physiological role of this system is to maintain NMDAR activity within safe limits, thereby protecting neural cells from excitotoxicity. Thus, cannabinoids may be able to control NMDAR overactivation-related neural dysfunctions; however, the major obstacles to the therapeutic utilization of these compounds are their psychotropic effects and negative influence on cognitive performance. Studies in humans have indicated that abuse of smoked cannabis can promote psychosis and even circumstantially precipitate symptoms ofschizophrenia, although the latter appears to require a prior vulnerability in the individual. It is possible that cannabinoids provoke psychosis/schizophrenia反映神经保护共有的机制：NMDAR活性的降低。建议通过减少谷氨酸前突触前释放或干扰突触后NMDAR调节的信号通路来产生这种作用。这种控制的功效要求内源性大麻素系统以与NMDAR信号强度成正比的方式应用其负面影响。因此，在错误的时间作用或对其受体发挥不适当影响的大麻素可能会导致NMDAR功能低下。本综述的目的是吸引读者对新描述的功能和物理CB1-NMDAR关联的注意，该功能和物理CB1-NMDAR关联可能阐明了快速有效地控制NMDAR活动所需的情况。这些机制的改变是否会增加NMDAR功能功能障碍，从而导致脆弱性schizophrenia将概述。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Brain Res. 2015 Oct 1622: 196-203 |
| PMID | 26133792 |
| 标题 | Hint1 knockout results in a compromised activation of protein kinase C gamma in the brain. |
| Abstract | 先前的研究暗示了组氨酸三合会核苷酸结合蛋白1（Hint1） 在the pathogenesis ofschizophrenia。蛋白激酶C伽马（PKC？）可能参与Hint1- 自PKC以来的发病机理？被确定为Hint1interacting protein. Recently, a debate was brought forward from the understanding howHint1affects the expression and activity of PKC? in the brain. In the present study, we useHint1敲除小鼠和生化分析，以定义Hint1on protein PKC?. Our data reveal thatHint1-deficiency in mouse brains led to increased protein levels of PKC? in the cortex and hippocampus, the striatum and thalamus and amygdala. Without stimulation, PKC? protein inHint1- 缺陷型大脑表现出的基础活性是由PKC的对照级磷酸化反映的？T514和T674在其激酶域。在心理刺激后，PKC的两个地点？T514和T674通过磷酸化在这些大脑结构中激活。但是，PKC部位的磷酸化水平？T674显然在Hint1-deficient mice compared to wild-type control. Thus, we conclude thatHint1deficiency leads to an increased protein level of PKC? in the brain and a compromised activation response of PKC? upon stimulation. These findings suggest an inhibitory role ofHint1on the protein PKC? in the brain and an impaired PKC?-mediated phosphorylation signal inHint1-deficient neuron. |
| SCZ Keywords | schizophrenia, schizophrenic |