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1.
Wan-Xia Xiong Guo-Xia Zhou Bei Wang Zhang-Gang Xue Lu Wang Hui-Chuan Sun Sheng-Jin Ge 《PloS one》2013,8(11)
Neurocognitive deficits arising from anesthetic exposure have recently been debated, while studies have shown that the phosphorylation of cyclic AMP response element-binding protein (CREB) in the hippocampus is critical for long-term memory. To better understand the neural effects of inhalational anesthetics, we studied the behavioral and biochemical changes in aged rats that were exposed to sevoflurane (Sev) and nitrous oxide (N2O) for 4 h. Eighteen-month-old rats were randomly assigned to receive 1.3% sevoflurane and 50% nitrous oxide/50% oxygen or 50% oxygen for 4 h. Spatial learning and memory were tested with the Morris water maze 48 h after exposure, and the results showed that sevoflurane–nitrous oxide exposure induced a significant deficit in spatial learning acquisition and memory retention. Experiments revealed that the cAMP and pCREB levels in the dorsal hippocampus were decreased in rats with anesthetic exposure in comparison with control rats 48 h after anesthesia as well as 15 min after the probe trial, but there were no significant differences in CREB expression. Besides these, the current study also found the DG neurogenesis significantly decreased as well as neuronal loss and neuronal apoptosis increased in the hippocampus of rats exposed to Sev+N2O. The current study demonstrated that down-regulation of cAMP/CREB signaling, decrease of CREB-dependent neurogenesis and neuronal survival in the hippocampus contributed to the neurotoxicity and cognitive dysfunction induced by general anesthesia with sevoflurane–nitrous oxide. 相似文献
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Neurochemical Research - Interleukin-1β (IL-1β) plays a critical role in the development of neuropathic pain through activation of Schwann cells (SCs) after nerve injury. Here, we applied... 相似文献
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α-Synuclein (αSYN) is genetically and neuropathologically linked to a spectrum of neurodegenerative diseases including Parkinson’s disease, dementia with Lewy bodies, and related disorders. Cognitive impairment is recapitulated in several αSYN transgenic mouse lines. However, the mechanisms of dysfunction in affected neurons are largely unknown. Here we measured neuronal activity induced gene products in the limbic system of αSYN transgenic mice upon fear conditioning (FC). Induction of the synaptic plasticity marker c-Fos was significantly reduced in the amygdala and hippocampus of (Thy1)-h[A30P]αSYN transgenic mice in an age-dependent manner. Similarly, the neuronal activity inducible polo-like kinase 2 (Plk2) that can phosphorylate αSYN at the pathological site serine-129 was up-regulated in both brain regions upon FC. Plk2 inductions were also significantly impaired in aged (Thy1)-h[A30P]αSYN transgenic mice, both in the amygdala and hippocampus. Plk2 inductions in the amygdala after FC were paralleled by a small but significant increase in the number of neuronal cell bodies immunopositive for serine-129 phosphorylated αSYN in young but not aged (Thy1)-h[A30P]αSYN transgenic mice. In addition, we observed in the aged hippocampus a distinct type of apparently unmodified transgenic αSYN profiles resembling synaptic accumulations of αSYN. Thus, the cognitive decline observed in aged αSYN transgenic mice might be due to impairment of neurotransmission and synaptic plasticity in the limbic system by distinct αSYN species. 相似文献
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Kyu Yun Jang Yo Na Kim Jun Sang Bae Myoung Ja Chung Woo Sung Moon Myoung Jae Kang Dong Geun Lee Ho Sung Park 《Translational oncology》2012,5(5):370-378
Background
The aim of this study is to investigate the prevalence and prognostic impact of β-catenin and cyclin D1 expression in colorectal carcinoma (CRC) patients.Method
We evaluated immunohistochemial expression of β-catenin and cyclin D1 using 2-mm cores from 220 CRC patients for tissue microarray, and its significance was statistically evaluated.Result
Positive expression of β-catenin and cyclin D1 was found in 72.5% (158 of 218 cases) and 59.4% (129 of 217 cases) of CRC patients, respectively. Expression of β-catenin was significantly correlated with tumor location (P = .017), differentiation (P = .010), lymph node metastasis (P = .032), preoperative carcinoembryonic antigen level (P = .032), and cyclin D1 expression (P = .005). Expression of cyclin D1 was significantly correlated with recurrence and/or metastasis (P = .004). In univariate analysis, β-catenin expression predicted more favorable overall survival (P = .022) and cyclin D1 expression predicted both more favorable overall survival and relapse-free survival (P = .004 and P = .006, respectively). Multivariate analysis showed that tumor stage and expression of cyclin D1 were independent prognostic factors significantly associated with overall survival and relapse-free survival.Conclusion
This study shows that expression of β-catenin and cyclin D1 is associated with favorable clinicopathologic variables and it is a clinically significant prognostic indicator for CRC patients. 相似文献7.
Renqiang Ma Yi Wei Xiaoming Huang Ran Fu Xi Luo Xiaolin Zhu Wenbin Lei Jugao Fang Huabin Li Weiping Wen 《PloS one》2013,8(7)
Background
Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3β) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3β, it is possible that inactivation of GSK3β may lead to excessive EZH2 expression in NPC.Method
We first examined the expression of EZH2 and phosphorylated GSK3β (p-GSK3β) by immunohistochemical staining in NPC samples. Then, we evaluated the interaction of GSK3β and EZH2 using immunoprecipitation and immune blot. Moreover, we determined the effect of inhibition of GSK3β activity on EZH2 expression and tumor invasiveness in NPC cell lines in vitro. Finally, we evaluated the invasive properties of NPC cells after knocking down EZH2 expression with EZH2 siRNA.Results
We found that expression of EZH2 correlated with phosphorylated GSK3β (p-GSK3β) at Ser 9 (an inactivated form of GSK3β) in human nasopharyngeal carcinoma (NPC) samples. We also provided evidence that GSK3β is able to interact with EZH2 using immunoprecipitation and immune blot. Furthermore, we found that inhibition of GSK3β activity can lead to upregulation of EZH2 in NPC cell lines in vitro, with enhanced local invasiveness. By knocking down EZH2 expression with EZH2 siRNA, we found that these invasive properties were EZH2 dependent.Conclusion
Our findings indicate that GSK3β inactivation may account for EZH2 overexpression and subsequent tumour progression, and this mechanism might be a potential target for NPC therapy. 相似文献8.
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Bonilla E Valero N Chacín-Bonilla L Pons H Larreal Y Medina-Leendertz S Espina LM 《Neurochemical research》2003,28(5):681-686
The effect of melatonin (MLT) on the brain levels of tumor necrosis factor alpha (TNF-) and interleukin-1 (IL-1) in Venezuelan equine encephalomyelitis (VEE) virus infection was determined. Brain homogenates from mice inoculated with 10 LD50 of VEE virus, untreated or treated with 500g MLT/kg body weight were assayed by ELISA to measure the levels of TNF- and IL-1. MLT was injected daily starting 3 days before and continuing to 7 days after virus inoculation. Infected mice treated with MLT showed decreased levels of TNF- when compared to the untreated infected mice on days 1, 3, 4, and 5 postinoculation (P < 0.001). In contrast, IL-1 levels increased from days 1 to 5 in the infected mice treated with MLT when compared with the untreated infected animals (P < 0.01). The results suggest that the protective effect of MLT on the VEE virus infection could be due, among other factors, to a decrease in TNF- synthesis along with an increase in the production of IL-1. 相似文献
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Zhaojin Wang Dan Chen Rui Zhang Shuhong An Zaifeng Zhang Qingyuan Ma 《Neurochemical research》2013,38(9):1895-1903
Protease-activated receptor-4 (PAR4) is localized in primary sensory neurons and is believed to implicate in the modulation of nociceptive mechanisms. The pro-inflammatory cytokine interleukin-1β (IL-1β) is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. Previous studies have shown that IL-1β enhances the expression of PAR4 in many cell types but the effect of this cytokine on primary sensory neuron PAR4 expression is less clear. In the present study, we evaluated in rat dorsal root ganglion (DRG) neurons the influence of IL-1β on PAR4 mRNA and protein levels after IL-1β intraplantar injection into the hind-paw or treatment of cultured DRG neurons. The expression of PAR4 in cultured DRG neurons was also assessed after treatment with IL-1β with pre-addition of phorbol-12-myristate 13-acetate (PMA, a PKC activator) or chelerythrine chloride (a PKC inhibitor). We found that IL-1β intraplantar injection into the hind-paw or long-term exposure of cultured DRG neurons to IL-1β significantly increased the proportion of DRG neurons expressing PAR4 immunoreactivity. Real-time PCR and western blotting showed that IL-1β treatment also significantly elevated PAR4 mRNA and protein levels in DRG neurons. This IL-1β effect was enhanced in DRG neurons when DRG cultures were pre-treatment with the PMA. But pre-incubation with chelerythrine chloride strongly inhibited the IL-1β-induced increase of PAR4 mRNA and protein levels. These results demonstrate that the expression of PAR4 mRNA and protein induced by IL-1β is PKC signaling pathway dependent. 相似文献
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The objective of this study was to investigate the possible association between the expression of transforming growth factor beta-1 (TGF-β1) and breast cancer type2 susceptibility protein (BRCA2) with clinical factors in breast cancer. TGF-β1, BRCA2, human epidermal growth factor receptor2 (HER2), estrogen receptor, and progesterone receptor protein levels were measured in 67 samples from breast cancer patients by immunohistochemistry. The expression of these proteins was correlated with various clinical factors including age, pathohistological grade and status of axillary lymph node implication. TGF-β1 and BRCA2 were expressed in breast cancer tissues and expression of HER2 and TGF-β1 was significantly correlated with BRCA2. The authors conclude that elevated expression of BRCA2 correlates with TGF-β1 and HER2 in breast cancer and these three factors act in synergy to promote cancer. Thus, detection of both TGF-β1 and BRCA2 may therefore assist in the prognosis and treatment of breast cancer. 相似文献
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Jon R. Ward Peter W. West Mark P. Ariaans Lisa C. Parker Sheila E. Francis David C. Crossman Ian Sabroe Heather L. Wilson 《The Journal of biological chemistry》2010,285(30):23147-23158
The processing and regulated secretion of IL-1β are critical points of control of the biological activity of this important pro-inflammatory cytokine. IL-1β is produced by both monocytes and macrophages, but the rate and mechanism of release differ according to the differentiation status and the origin of these cells. We aimed to study the control of processing and release in human blood monocytes and human monocyte-derived macrophages. Toll-like receptor (TLR)-induced IL-1β production and release were investigated for dependence upon caspase-1, P2X7 receptor activation, and loss of membrane asymmetry associated with microvesicle shedding. TLR agonists induced P2X7 receptor-dependent IL-1β release in both monocytes and macrophages; however, only monocytes also showed P2X7 receptor-independent release of mature IL-1β. Furthermore, in monocytes ATP-mediated PS exposure could be activated independently of IL-1β production. Release of IL-1β from monocytes showed selectivity for specific TLR agonists and was accelerated by P2X7 receptor activation. Human monocytes released more IL-1β/cell than macrophages. These data have important implications for inflammatory diseases that involve monocyte activation and IL-1 release. 相似文献
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Shi-gao Yang Shao-wei Wang Min Zhao Ran Zhang Wei-wei Zhou Ya-nan Li Ya-jing Su He Zhang Xiao-lin Yu Rui-tian Liu 《PloS one》2012,7(11)
Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into β-amyloid (Aβ); the peptide likely contributes to development of Alzheimer’s disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the β-proteolytic site on APP and Aβ N-terminal. The S1 peptide significantly reduced Aβ levels in vitro and in vivo and inhibited Aβ cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Aβ burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Aβ generation and inhibiting Aβ cytotoxicity. 相似文献
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Purinergic Signalling - The pro-inflammatory cytokine IL-1β is a secreted protein that is cleaved by caspase-1 during inflammasome activation upon recognition of internal and external insults... 相似文献
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Molaei Pejman Vaseghi Salar Entezari Maliheh Hashemi Mehrdad Nasehi Mohammad 《Neurochemical research》2021,46(8):2154-2166
Neurochemical Research - Cholestasis is a bile flow reduction that is induced following Bile Duct Ligation (BDL). Cholestasis impairs memory and induces apoptosis. Apoptosis consists of two... 相似文献
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Susanna Leskela Ana Serrano Hortensia de la Fuente Ana Rodríguez-Mu?oz Ana Ramos-Levi Miguel Sampedro-Nu?ez Francisco Sánchez-Madrid Roberto González-Amaro Mónica Marazuela 《PloS one》2015,10(4)
Introduction
Patients with autoimmune thyroid disease (AITD) show defects in their immune-regulatory mechanisms. Herein we assessed the expression and function of galectin-1 and galectin-9 (Gal-1, Gal-9) in dendritic cells (DCs) from patients with AITD.Materials and Methods
Peripheral blood samples from 25 patients with Graves’ disease (GD), 11 Hashimoto’s thyroiditis (HT), and 24 healthy subjects were studied. Thyroid tissue samples from 44 patients with AITD and 22 patients with goiter were also analyzed. Expression and function of Gal-1 and Gal-9 was assessed by quantitative RT-PCR, immunofluorescence and flow cytometry.Results
A diminished expression of Gal-9, but not of Gal-1, by peripheral blood DCs was observed in GD patients, mainly in those with Graves´ ophthalmopathy, and a significant negative association between disease severity and Gal-9 expression was detected. In addition, the mRNA levels of Gal-9 and its ligand TIM-3 were increased in thyroid tissue from AITD patients and its expression was associated with the levels of Th1/Th12/Th17 cytokines. Immunofluorescence studies proved that intrathyroidal Gal-9 expression was confined to DCs and macrophages. Finally, in vitro functional assays showed that exogenous Gal-9 had a suppressive effect on the release of Th1/Th2/Th17 cytokines by DC/lymphocyte autologous co-cultures from both AITD patients and healthy controls.Conclusions
The altered pattern of expression of Gal-9 in peripheral blood DCs from GD patients, its correlation with disease severity as well as its ability to suppress cytokine release suggest that Gal-9 could be involved in the pathogenesis of AITD. 相似文献17.
Zhou C Qi C Zhao J Wang F Zhang W Li C Jing J Kang X Chai Z 《Neurochemical research》2011,36(6):1116-1123
Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine that plays a key role in the injuries and diseases of
the central nervous system (CNS). A voltage-gated Na+ channel is essential for the excitability and electrical properties of neurons. However, it is not known whether IL-1β directly
affects the central Na+ channels. In the present study, we examined the effects of IL-1β on Na+ currents in cultured cortical neurons using patch-clamp recording. Our results showed that IL-1β suppressed Na+ currents through its receptor in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and
inactivation. PKC and then p38 MAPK were involved in this inhibition. The spike amplitude was also inhibited by IL-1β in the
doses that decreased the Na+ currents. Our findings revealed the inhibition of chronic IL-1β treatment on voltage-gated Na+ channels in the CNS, and showed that the action potential (AP) amplitude was reduced by IL-1β due to a decrease of Na+ currents. 相似文献
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Rafael Fernandes Zanin Letícia Scussel Bergamin Fernanda Bueno Morrone Robson Coutinho-Silva Angela Terezinha de Souza Wyse Ana Maria Oliveira Battastini 《Purinergic signalling》2015,11(4):463-470
Elevated plasma levels of homocysteine (Hcy) are associated with the development of coronary artery disease (CAD), peripheral vascular disease, and atherosclerosis. Hyperhomocysteinemia is likely related to the enhanced production of pro-inflammatory cytokines including IL-1β. However, the mechanisms underlying the effects of Hcy in immune cells are not completely understood. Recent studies have established a link between macrophage accumulation, cytokine IL-1β, and the advance of vascular diseases. The purpose of the present study is to investigate the effects of Hcy on IL-1β secretion by murine macrophages. Hcy (100 μM) increases IL-1β synthesis via enhancement of P2X7 expression and NF-ĸB and ERK activation in murine macrophages. In addition, the antioxidant agent N-acetylcysteine (NAC) reduces NF-κB activation, ERK phosphorylation, and IL-1β production in Hcy-exposed macrophages, indicating the importance of ROS in this pro-inflammatory process. In summary, our results show that Hcy may be involved in the synthesis and secretion of IL-1β via NF-ĸB, ERK, and P2X7 stimulation in murine macrophages. 相似文献
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《Biochemical and biophysical research communications》1997,238(3):880-885
The principal regulator of parathyroid hormone (PTH) secretion is ionized calcium, but other factors are also known to modulate PTH secretion, such as vitamin D, estrogen, and recently inorganic phosphate. Interleukin-1 (IL-1) possesses a wide variety of biological activities and is produced by leukocytes as well as by various other cells including cells from endocrine tissues and might play a role as a paracrine factor in the control of PTH secretion. We investigated the effectin vitroof IL-1β on PTH release, PTHmRNA and the mRNA for the extracellular calcium-sensing receptor (CaR) levels in preparations of bovine parathyroid cells. PTH secretion from cultured parathyroid tissue slices was significantly inhibited in a medium containing IL-1β at a concentration of 2000 pg/ml (PTH in % of control: 63.5 ± 5.3), n=10 (p<0.01). The inhibitory effect of IL-1β was not found in preparations of dispersed cells. The inhibitory effect of IL-1β could be counteracted by the IL-1 receptor antagonist (IL-1ra), indicating that the inhibitory effect was mediated through the specific IL-1 receptor on the parathyroid cells. IL-1β (2000 pg/ml) up-regulated CaRmRNA levels to 180% of control, whereas no change in PTHmRNA was found. IL-1ra abolished the upregulating effect of IL-1β on the CaRmRNA. This study demonstrates a direct effectin vitroof IL-1β on PTH secretion from bovine parathyroid glands, an effect which may be mediated at least in part through the specific IL-1 receptor causing an upregulation of the calcium-sensing receptor mRNA. IL-1 might therefore play a role as a auto- and/or paracrine factor in the regulation of the PTH secretion. 相似文献
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Lan Zhen Meng Zhaoyou Lian Biyao Liu Mengying Sun Tao Sun Huan Liu Zhi Hu Zhenxin Guo Qiang Zhang Jiqiang 《Neurochemical research》2021,46(5):1188-1202
Neurochemical Research - Ovarian estrogens (mainly 17β estradiol, E2) have been involved in the regulation of the structure of hippocampus, the center of spatial memory. In recent years, high... 相似文献