Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.

Environmental cues associated with morphine modulate release of glutamate and γ-aminobutyric acid in ventral subiculum

Objective To investigate whether environmental cues associated with different properties of morphine could regulate the extracellular levels of glutamate and y-aminobutyric acid （GABA） in the hippocampal ventral subiculum, which play a critical role in the reinstatement of drug-seeking behavior induced by environmental cues. Methods Conditioning place preference （CPP） and conditioning place aversion （CPA） models were used to establish environment associated with rewarding and aversive properties of morphine respectively. Microdialysis and high performance liquid chromatography were used to measure the extracelluar level of glutamate and GABA in the ventral subiculum under these environmental cues. Results Exposure to the environmental cues associated with rewarding properties of morphine resulted in a decrease （approximately 11%） of extracellular level of GABA in ventral subiculum, and exposure to the environmental cues associated with aversive properties of morphine resulted in an increase （approximately 230%） of extracellular level of glutamate in ventral subiculum. Conclusion Environmental cues associated with different properties of morphine modulate the release of distinct neurotransmitters in the hippocampal ventral subiculum possibly through different neural circuit.

Effect of Propofol on Glutamate and γ-aminobutyric Acid Release from Rat Hippocampal Synaptosomes

To investigate the effect of propofol on the release of glutamate and γ-aminobutyric acid （GABA） from rat hippocampal synatosomes, synaptosomes was made from hippocampus and incubated with artificial cerebrospinal fluid （aCSF）. With the experiment of Ca^2＋-dependent release of glutamate and GABA, dihydrokainic acid （DHK） and nipectic acid were added into aCSF. For the observation of Ca^2＋-independent release of glutamate and GABA, no DHK, nipectic acid and Ca^2＋ were added from aCSF. The release of glutamate and GABA were evoked by 20 μmol/L veratridine or 30 mmol/L KCh The concentration of glutamate and GABA in aCSF was measured by using high-performance liquid chromatography （HPLC）. 30, 100 arid 300 μmol/L propofol significantly inhibited veratridine-evoked Ca^2＋-dependent release of glutamate and GABA （P〈0. 01 or P〈0. 05）, However, propofol showed no effect on elevated KCl-evoked Ca^2＋-dependent release of glutamate and GABA （P〉0, 05）, Veratridine or elevated KCI evoked Ca^2＋-independent release of glutamate and GABA was not affected significantly by propofol （P〉0.05）. Propofol could inhibit Ca^2＋- dependent release of glutamate and GABA, However, it has no effect on the Ca^2＋-independent release of glutamate and GABA,

Evolution of neurotransmitter gamma-aminobutyric acid,glutamate and their receptors

Gamma-aminobutyric acid(GABA)and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals,insects,round worm,and platyhelminths,while their receptors are quite diversified across different animal phyla.However,the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive,and antagonistic interactions between GABA and glutamate signal transduction systems,in particular,have begun to attract significant attention.In this review,we summarize the extant results on the origin and evolution of GABA and glutamate,as well as their receptors,and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors.We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter(EAAT),a transport protein,which plays an important role in the GABA-glutamate“yin and yang”balanced regulation.Finally,based on current advances,we propose several potential directions of future research.

Developmental changes of glutamate acid decarboxylase 67 in mouse brain after hypoxia ischemia

Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature （P21, P60） and immature （P5, P9） brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia （HI） insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that （15.6±7.0）% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.

Evolution of neurotransmitter gamma-aminobutyric acid, glutamate and their receptors

Gamma-aminobutyric acid （GABA） and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite diversified across different animal phyla. However, the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive, and antagonistic interactions between GABA and glutamate signal transduction systems, in particular, have began to attract significant attention. In this review, we summarize the extant results on the origin and evolution of GABA and glutamate, as well as their receptors, and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors. We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter （EAAT）, a transport protein, which plays an important role in the GABA-glutamate ＂yin and yang＂ balanced regulation. Finally, based on current advances, we propose several potential directions of future research.

Sodium glutamate and gamma-aminobutyric acid affect iron metabolism in the rat caudate putamen

Glutamic acid and gamma-aminobutyric acid （GABA） influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 （DMT1） and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1 （-IRE）] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1 （-IRE） expression was significantly reduced, but hephaestin expressiori was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMTI（-IRE） and decreasing hephaestin expression. In addition, GABA decreased DMT1 （-IRE） expression in the caudate putamen.

Altered expression of metabotropic glutamate receptor 1 alpha after acute diffuse brain injury Effect of the competitive antagonist 1-aminoindan-1, 5-dicarboxylic acid

The diffuse brain injury model was conducted in Sprague-Dawley rats, according to Marmarou＇s free-fall attack. The water content in brain tissue, expression of metabotropic glutamate receptor la mRNA and protein were significantly increased after injury, reached a peak at 24 hours, and then gradually decreased. After treatment with the competitive antagonist of metabotropic glutamate receptor la, （RS）-l-aminoindan-1,5-dicarboxylic acid, the water content of brain tissues decreased between 12-72 hours after injury, and neurological behaviors improved at 2 weeks. These experimental findings suggest that the 1-aminoindan-1, 5-dicarboxylic acid may result in marked neuroprotection against diffuse brain injury.

Expression of metabotropic glutamate receptor 1a in a rat cortical neuronal model of in vitro mechanical injury and the effects of its competitive antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid

The present study established a rat cortical neuronal model of in vitro mechanical injury. At 30 minutes after injury, the survival rate of the injured cortical neurons was decreased compared with normal neurons, and was gradually decreased with aggravated degree of injury. Reverse transcription-polymerase chain reaction results showed that at 1 hour after injury, there was increased expression of metabotropic glutamate receptor la in cortical neurons. Immunohistochemical staining results showed that at 30 minutes after injury, the number of metabotropic glutamate receptor 1a-positive cells increased compared with normal neurons. At 12 hours after injury, lactate dehydrogenase activity in the （RS）-l-aminoindan-1, 5-dicarboxylic acid （AIDA）-treated injury neurons was si[jnificantly decreased than that in the pure injury group. At 1 hour after injury, intracellular free Ca＂＋ concentration was markedly decreased in the AIDA-treated injury neurons than that in the pure injury neurons. These findings suggest that after mechanical injury to cortical neurons, metabotropic glutamate receptor la expression increased. The resulting increase in intracellular free Ca2＋ concentration was blocked by AIDA, indicating that AIDA exhibits neuroprotective effects after mechanical injury.

Effects of progesterone on glutamate transporter 2 and gamma-aminobutyric acid transporter 1 expression in the developing rat brain after recurrent seizures

Seizures were induced by flurothyl inhalation. Rats were intramuscularly treated with progesterone after each seizure. Results demonstrated that glutamate transporter 2 and y-aminobutyric acid transporter 1 expression levels were significantly increased in the cerebral cortex and hippocampus of the developing rat brain following recurrent seizures. After progesterone treatment, glutamate transporter 2 protein expression was upregulated, but ^-aminobutyric acid transporter 1 levels decreased. These results suggest that glutamate transporter 2 and y-aminobutyric acid transporter 1 are involved in the pathological processes of epilepsy. Progesterone can help maintain a balance between excitatory and inhibitory systems by modulating the amino acid transporter system, and protect the developing brain after recurrent seizures.

Effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in prefrontal lobe and hippocampus of depressive rats

Objective:To investigate the effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in the prefrontal lobe and hippocampus of depressive rats.Methods:100 healthy SD rats were divided into healthy control group, blank control group and Eritram group (low dose group, medium dose group and high dose group), 20 rats in each group. The depression model of rats in blank control group and Salvia miltiorrhiza group was established. After the completion of the model, rats in the blank control group were injected with normal saline and rats in the Eritrean group were injected with high, medium and low doses of Eritrean injection respectively. After 21 days of continuous administration, the total distance of spontaneous activity, the immobility time of forced swimming, the levels of gamma-aminobutyric glutamate (GABA), glutamate (Glu) and Toll-like receptor 4 (TLR-4) protein in prefrontal lobe and hippocampal neurons were measured and compared. Pearson correlation test was used to analyze the correlation between TLR4 and GABA, Glu levels in depressive rats.Results: Compared with the healthy control group, the total spontaneous activity distance of the blank control group and Eritrean group decreased significantly, and the immobility time of forced swimming increased significantly (P<0.05). There was a significant difference between the blank control group and Eritrean group (P<0.05). The rats in Eritrean group spontaneously survived with the increase of dose. The total distance increased, while the immobility time of forced swimming decreased (P<0.05). Compared with the healthy control group, the levels of GABA in the prefrontal lobe and hippocampus of rats in blank control group and Eritrean group decreased significantly, the levels of Glu and TLR4 increased significantly, and the levels of GABA in Eritrean group were higher than those in blank control group, and the levels of Glu and TLR4 were lower than those in blank control group. TLR4 and TLR4 decreased significantly (P<0.05). Pearson correlation test showed that TLR4 was negatively correlated with GABA and positively correlated with Glu (P<0.05). Conclusion: Eritrean can reduce the effects of depression on the neurogenesis of prefrontal lobe and hippocampal neurons and the balance of gamma-aminobutyric acid and glutamate in rats. The mechanism is that Eritrean can increase the level of GABA and decrease the level of Glu by antagonizing Toll-like receptor 4, thus exerting the neuroprotective effect of prefrontal lobe and hippocampal neurons.

Methods for the Determination of Stable Isotopes of Carbon and Nitrogen Directly in Valine, Proline, Glutamine, and Glutamic Acid

Amino acids are very important compounds for the body and are involved in important functions that keep us healthy. Amino acids are essential components such as valine, proline, glutamine and glutamic acid. They can be synthesized either naturally or artificially. To examine the metabolism and regulate the synthesis process, compounds labeled with nitrogen or carbon isotopes need to be used. These isotopic compounds allow for more extensive research and enable studies that would otherwise be impossible. However, their use is dependent on the availability of simple, efficient methods for isotopic analysis. Currently, the determination of the atomic fraction of carbon and nitrogen isotopes is only possible through their conversion into molecular nitrogen or carbon monoxide or carbon dioxide. This leads to the loss of information about isotopic enrichment in specific centers of the molecule. This article explores a new direct approach to determining the atomic fraction of carbon and nitrogen isotopes in the isotope-modified or identical centers of these compounds. This method eliminates the transfer process and dilution due to nitrogen and carbon impurities. It is now possible to simultaneously determine the atomic fraction of nitrogen and carbon isotopes in the research substance. This method can be applied to amino acids, making it an effective tool for proposing new research methods. Several articles [1] [2] [3] have proposed similar methods for organic compounds and amino acids.

Construction of Escherichia coli by Metabolic Engineering for Synthesis of Mesaconic Acid

Mesaconic acid has a special chemical structure and can undergo a series of reactions such as polymerization and addition. It is an important chemical intermediate and widely used in material, chemical and other industries. The chemical synthesis of mesaconic acid requires nitric acid, which is dangerous and harmful to the environment. The production of mesaconic acid by microbial fermentation has the characteristics of low raw material price, high efficiency and strong specificity, and thus a strong industrial application prospect. Mesaconic acid is an intermediate product of glutamic acid degradation pathway of microorganisms such as Clostridium tetani. However, at present, few reports have been conducted on the production of mesaconic acid by metabolic engineering microorganisms. In this study, glutamate mutase(GLM) and 3-methylaspartate ammonialyase(MAL) from C. tetani were recombined and expressed in Escherichia coli, and the obtained strain, BL21(DE3)/pETDuet-1-MAL-mutS-mutE, achieved the yield of mesaconic acid of 1.06 g/L. Compared with the wild type, the yields of mesaconic acid from mutants G133A and G133S increased by 21% and 16%, respectively. After 24 h of flask fermentation, the yields of mesaconic acid reached 1.28 and 1.23 g/L, respectively. This study can provide reference for microbial synthesis of mesaconic acid.

Effects of Addition of Amino Acids or Soybean Phospholipid in Diet on Slaughter Performance and Meat Quality of Pigs

[Objectives]The study aims to discuss the effects of addition of arginine and glutamic acid or soybean phospholipid,vitamin E and yeast selenium in diet on the slaughter performance and meat quality of long(white)×large(York)binary hybrid pigs.[Methods]27 long×large castrated hybrid boars with the body weight of(54.4±0.15)kg were randomly divided into 3 groups,with 3 replicates per group and 3 pigs per replicate.Group A was the control group,in which the pigs were fed basal diet;in group B,0.8%arginine and 0.60%glutamate were added to the basal diet;in group C,75 g of soybean phospholipid,20 g of vitamin E and 8 g of yeast selenium were added to every 100 kg of the basal diet.The trial period was 60 d.After the experiment was ended,one test pig with similar body weight was selected from each replicate for slaughter and meat determination.[Results]The average weight gain and eye muscle area of the pigs in group B were significantly higher than those in group C(P<0.05),and also showed an increasing trend compared with group A,but there was no statistically significant difference(P>0.05);there was no significant difference between group B or C and group A in the average weight gain and eye muscle area(P>0.05).There was no significant difference in other slaughter performance between the three groups(P>0.05).Besides,there was also no significant difference in the content of various amino acids,total amino acids and total umami amino acids between the three groups(P>0.05).The inosine content in the longissimus dorsi muscle and muscle cooking loss of binary hybrid pigs in group C were significantly better than those in group B(P<0.05),and also had a tendency to be better than those in group A,but there was no significant difference(P>0.05);there was no significant difference between group B or C and group A in the inosine content and muscle cooking loss of the pigs(P>0.05).In addition,there was no significant difference in other meat traits and chemical composition of the longissimus dorsi muscle between group B or C and group A(P>0.05).[Conclusions]The addition of arginine and glutamic acid or soybean phospholipid,vitamin E and yeast selenium in diet had no significant effect on the growth rate,slaughter performance and meat traits of long×large binary hybrid pigs.

温胆汤含药血清对10 mmol/L谷氨酸环境下星型胶质细胞PI3K、Akt、mTOR表达的影响

目的 探讨温胆汤含药血清对10 mmol/L谷氨酸诱导的大鼠星型胶质细胞凋亡、周期及磷脂酰肌醇3-激酶(phosphoinositide 3-kinase, PI3K)、蛋白激酶B(protein kinase B,Akt)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)表达的影响。方法 将60只SPF级SD雄性大鼠随机分为5组,其中正常组20只,氯氮平组和温胆汤高、中、低剂量组各10只。正常组予20 g/kg 0.9%氯化钠溶液灌胃,氯氮平组予氯氮平原药20 mg/kg灌胃,温胆汤高、中、低剂量组分别予40、20、10 g/kg温胆汤灌胃,1次/d,共8 d。处死大鼠后取血,离心取血清,灭活除菌,EP管分装备用。将大鼠星型胶质细胞分为正常血清组、模型血清组,氯氮平含药血清组和温胆汤高、中、低剂量含药血清组,除正常血清组外,其余各组予10μmol/mL谷氨酸处理48 h后,流式细胞仪检测细胞凋亡和细胞周期;Western bloting、Real-time PCR分别测定细胞PI3K、Akt、mTOR蛋白和mRNA表达。结果 温胆汤含药血清可明显降低谷氨酸环境下大鼠星型胶质细胞凋亡率(P<0.01)和G0/G1期细胞占比(P<0.05),升高S期及G2/M期细胞占比;降低细胞P-P13K/P13K、P-ATK/AKT、P-mTOR/mTOR蛋白表达比值(温胆汤低剂量血清组除外,P<0.05)和细胞PI3K、Akt、mTOR mRNA表达(温胆汤低剂量血清组除外,P<0.01)。结论 温胆汤含药血清可有效调节大鼠星形胶质细胞PI3K、Akt、mTOR表达,达到保护神经细胞的目的,这可能是温胆汤治疗精神分裂症的作用机制之一。

基于稻谷加温加湿技术的γ-氨基丁酸富化

目的:提高糙米品质。方法:以γ-氨基丁酸(GABA)含量和谷氨酸脱羧酶活性作为指标,研究富化条件对GABA含量的影响;基于最优参数,通过分析富化过程中籽粒各部位GABA含量,揭示其迁移规律;最后分析该法对糙米品质的影响,并与浸泡法对比。结果:原料水分含量14.5%,富化温度65℃,最终水分含量20%,富化时间5 h时,GABA含量最高。富化过程中,GABA主要在糠层生成,在生成的同时向内部迁移,各碾减率的糙米GABA含量均在5 h达到峰值,但迁移率在4 h后趋于稳定,胚乳部分的GABA迁移率最高可达87.1%。与浸泡法相比,加温加湿法富化的糙米偏黄,爆腰率较低,米饭更柔软。结论:加温加湿法优于浸泡法,可用于制备高GABA含量的糙米和精米。

基于纳米银/聚L-谷氨酸修饰玻碳电极的电化学传感器用于泡菜中亚硝酸钠含量的测定

采用电沉积和电聚合的方式,将纳米银和L-谷氨酸修饰在玻碳电极上,制得纳米银/聚L-谷氨酸修饰玻碳电极(Poly-L-Glu/Nano-Ag/GCE)。以0.2 mol·L^(-1)磷酸盐缓冲溶液(pH 7.0)为支持电解质,以Poly-L-Glu/Nano-Ag/GCE为工作电极,饱和甘汞电极为参比电极,铂电极为辅助电极,在最佳检测条件下,采用循环伏安法进行测定。结果表明:Poly-L-Glu/Nano-Ag/GCE对亚硝酸钠具有较好的选择性,亚硝酸钠的浓度在4.14×10^(-6)~1.35×10^(-3) mol·L^(-1)内与对应的氧化峰电流的绝对值呈线性关系,检出限(3s/k)为4.14×10^(-7) mol·L^(-1),并且该电极的制备方法具有较好的重复性。将PolyL-Glu/Nano-Ag/GCE用于泡菜样品中亚硝酸钠的测定,检出量为1.33×10^(-5) mol·L^(-1),加标回收率为98.9%~103%。

谷氨酸、CRP及S-100β蛋白水平与脑出血患者预后的关系

目的:分析谷氨酸、C反应蛋白(CRP)及S-100β蛋白水平与脑出血患者预后的关系。方法:选择2021年1月—2023年12月南昌大学第四附属医院收治的80例脑出血患者,患者入院后采集血样,测定血清谷氨酸、CRP及S-100β蛋白水平。随访90 d,采用格拉斯哥预后量表(GPS)进行预后评价,根据GPS评分分为预后不良组(1~3分)、预后良好组(4~5分),比较两组谷氨酸、CRP及S-100β蛋白水平,分析谷氨酸、CRP及S-100β蛋白水平与预后的相关性,采用受试者操作特征(ROC)曲线分析这些生物标志物对患者预后预测的价值。结果:在80例脑出血患者中,预后不良发生率为43.75%(35/80)。预后不良组血清谷氨酸、CRP及S-100β蛋白水平均高于预后良好组(P<0.05)。点二列相关系数分析结果显示,谷氨酸、CRP及S-100β蛋白与预后呈正相关(r=0.709、0.764、0.654,P<0.05)。Pearson相关系数分析显示,谷氨酸、CRP与S-100β蛋白呈正相关(r=0.361、0.431,P<0.001)。ROC曲线显示,谷氨酸、CRP、S-100β蛋白对患者预后预测的AUC分别为0.912、0.945、0.881,有一定预测价值。结论:谷氨酸、CRP及S-100β蛋白水平与脑出血患者的预后呈正相关,并具有一定的预测价值,在评估脑出血患者的预后时,这些可作为重要的参考指标之一。

湿法热解法制备L-焦谷氨酸的工艺优化研究

采用湿法热解法,以L-谷氨酸为原料,探究L-焦谷氨酸的制备工艺条件。通过单因素和正交试验对反应的条件进行优化,确定了制备L-焦谷氨酸的最佳工艺条件是反应时间4 h、加水量15 g、反应温度150℃,此时所得L-谷氨酸的转化率为97.37%。这种方法是用水作为反应载体,无需催化剂与压力等条件,既节能减排,又产量高,为清洁高效生产L-焦谷氨酸提供了一定的理论指导和实验数据参考。

泛癌分析揭示SREK1在低级别胶质瘤中促进CD274表达

目的剪接调节谷氨酸和富赖氨酸的蛋白质1(SREK1)在多种肿瘤中的泛癌分析,揭示SREK1在泛癌中的作用。方法利用在线数据库GEPIA 2、TIMER 2.0、TISIDB和cBioPortal分析SREK1表达对肿瘤患者预后的影响、在低级别胶质瘤(LGG)肿瘤组织中的表达、遗传变异的特征及其表达对肿瘤组织中免疫细胞的浸润和免疫—肿瘤靶基因的相关性分析。结果LGG肿瘤组织中,SREK1表达与记忆B细胞、活化的CD4+T细胞、Th2细胞、中性粒细胞、NKT细胞以及单核细胞和CD56dimNK细胞的浸润存在相关性(P均<0.05)。SREK1与免疫—肿瘤靶基因如信号传导及转录激活蛋白3(STAT3)、Ⅰ型干扰素受体1(IFNAR1)、核受体亚家族3C组成员1(NR3C1)和表皮生长因子受体(EGFR)、表面抗原分化簇274(CD274)等表达在LGG中均呈正相关(P均<0.05)。结论SREK1是LGG患者的危险因子之一,可能通过促进CD274的表达来加剧LGG的进展。