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nisin及大黄复方对子宫内膜炎大鼠血清中MMP-2和MMP-9活性的影响 总被引：3，自引：3，他引：0
为研究乳酸链球菌素(nisin)及大黄复方对患大鼠子宫内膜炎血清中基质金属蛋白酶-2、基质金属蛋白酶-9(MMP-2、MMP-9)的作用,构建大鼠子宫内膜炎模型,将280只SD大鼠随机分为nisin组、低、中、高剂量大黄复方组、阳性对照组、生理盐水组以及模型组,建子宫内膜炎模型前0h和建模后24、48、72h,用ELISA试剂盒检测各试验组中基质金属蛋白酶(MMPs)和基质金属蛋白抑制物(TIMPs)的变化情况来确定治疗效果。结果表明:1)在0~72h之间,模型组中,MMP-9和TIMP-1的质量浓度显著低于生理盐水组(P0.05),且MMP-2和TIMP-2的质量浓度逐渐降低;2)nisin和高剂量大黄复方组中MMP-9、TIMP-1、MMP-2和TIMP-2的质量浓度均显著高于生理盐水组(P0.05),其中以nisin组和高剂量大黄复方组效果最佳。由此可见,nisin和高剂量大黄复方能显著提高子宫内膜炎大鼠血清中TIMP-1和TIMP-2的表达,抑制MMP-9和MMP-2的活性而发挥调控子宫内生理机能的作用,表明nisin、中、高剂量大黄复方对MMP-9、TIMP-1和MMP-2的质量浓度具有正调控作用。 相似文献
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Chung KK Thomas B Li X Pletnikova O Troncoso JC Marsh L Dawson VL Dawson TM 《Science (New York, N.Y.)》2004,304(5675):1328-1331
Parkin is an E3 ubiquitin ligase involved in the ubiquitination of proteins that are important in the survival of dopamine neurons in Parkinson's disease (PD). We show that parkin is S-nitrosylated in vitro, as well as in vivo in a mouse model of PD and in brains of patients with PD and diffuse Lewy body disease. Moreover, S-nitrosylation inhibits parkin's ubiquitin E3 ligase activity and its protective function. The inhibition of parkin's ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in these disorders by impairing the ubiquitination of parkin substrates. 相似文献
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李洪涛 《河北北方学院学报(自然科学版)》2012,28(3):59-61,65
目的探讨乳腺肿瘤中基质金属蛋白酶（MMP）-13的表达及其与其他生物学指标和临床预后的关系。方法采用组织芯片及免疫组织化学SP法检测183例乳腺癌组织和30例乳腺良性疾病组织中MMP-13、ER、PR、HER2、MMP-2、MMP9、表皮生长因子受体（EGFR）、基质金属蛋白酶组织抑制因子TIMP-1、TIMP-2的表达并分析相互关系,同时分析MMP-13与肿瘤临床病理分期、淋巴结转移状态、组织学分级、肿瘤大小、年龄、月经状态、病理类型、雌孕激素受体状态以及临床预后等的关系。结果MMP-13的表达与TIMP-1、TIMP-2均呈负相关,与HER2的表达呈正相关,而与ER、PR、MMP-2、MMP-9、EGFR的表达水平不相关。MMP-13的表达与淋巴结转移和高组织学分级相关（均P〈0．01）。MMP-13低表达组10年生存率与高表达组10年生存率差异有统计学意义（98．4％vs68．3％,P〈0．01）。结论MMP-13蛋白与浸润性乳腺癌的侵袭和转移相关,可作为判断预后不良的指标。 相似文献
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Mannick JB Hausladen A Liu L Hess DT Zeng M Miao QX Kane LS Gow AJ Stamler JS 《Science (New York, N.Y.)》1999,284(5414):651-654
Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways. 相似文献
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Nitric oxide acts substantially in cellular signal transduction through stimulus-coupled S-nitrosylation of cysteine residues. The mechanisms that might subserve protein denitrosylation in cellular signaling remain uncharacterized. Our search for denitrosylase activities focused on caspase-3, an exemplar of stimulus-dependent denitrosylation, and identified thioredoxin and thioredoxin reductase in a biochemical screen. In resting human lymphocytes, thioredoxin-1 actively denitrosylated cytosolic caspase-3 and thereby maintained a low steady-state amount of S-nitrosylation. Upon stimulation of Fas, thioredoxin-2 mediated denitrosylation of mitochondria-associated caspase-3, a process required for caspase-3 activation, and promoted apoptosis. Inhibition of thioredoxin-thioredoxin reductases enabled identification of additional substrates subject to endogenous S-nitrosylation. Thus, specific enzymatic mechanisms may regulate basal and stimulus-induced denitrosylation in mammalian cells. 相似文献
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VEGF、P-2、MMP-9在乳腺癌组织中的表达及其对侵袭和转移的影响 总被引：2，自引：1，他引：2
目的探讨血管内皮细胞生长因子(VEGF),基质金属蛋白酶2、9(MMP-2、MMP-9)在乳腺良性病变及乳腺癌组织中的表达及其对侵袭和转移的影响.方法应用免疫组化SP法检测10例乳腺良性病变及29例乳腺癌组织中VEGF、MMP-2和MMP-9的表达.结果乳腺癌组织中VEGF、MMP-2和MMP-9的阳性表达率分别为79.3%(23/29),96.6%(28/29)和89.7%(26/29),与乳腺良性病变组织中VEGF、MMP-2、MMP-9的阳性表达率分别为30.0%(3/10),40.0%(4/10)和30.0%(3/10)相比较,二者的差异有显著的统计学意义(P＜0.01).VEGF、MMP-2和MMP-9的表达与乳腺癌淋巴结转移呈中度正相关.乳腺癌组织中VEGF与MMP-2、MMP-9的表达呈中度正相关,MMP-2与MMP-9的表达也呈中度正相关.结论VEGF、MMP-2及MMP-9的高表达与乳腺癌的浸润和转移密切相关,有可能成为判断乳腺癌侵袭和转移的有价值的指标. 相似文献
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目的 研究蛹虫草多糖抗乳腺癌转移的作用及机制。方法 30只小鼠随机分为3组,分别为模型组、蛹虫草多糖低剂量组（20 mg/kg）和蛹虫草多糖高剂量组（80 mg/kg）,所有动物采用尾静脉接种4T1乳腺癌细胞建立乳腺癌肺转移模型,后2组接种后连续腹腔注射给予蛹虫草多糖15 d。以肺组织表面的肿瘤结节数、血清MMP-2和MMP-9含量、肺组织病理为检测指标;采用CCK8法检测蛹虫草多糖对4T1细胞增殖的影响;采用Caspase-3/7检测试剂盒测定细胞凋亡情况。结果 与模型组比较,蛹虫草多糖高剂量组能够明显降低小鼠肺部的肿瘤结节数（P<0.01）;与模型组比较,蛹虫草多糖高剂量组能够显著降低血清MMP-2和MMP-9的含量（P<0.01）;显微镜下发现,蛹虫草多糖高剂量组的肺组织肿瘤转移灶体积和数量均少于模型组。蛹虫草多糖对乳腺癌4T1细胞增殖具有浓度依赖性趋势的抑制作用,半数抑制浓度（IC50）为0.092 mg/mL;与溶媒组比较,0.10 mg/mL和0.20 mg/mL的蛹虫草多糖可以显著增加Caspase-3/7的表达（P<0.01）。结论 蛹虫草多糖可抑制乳腺癌肺转移,其作用机制可能与抑制MMP-2和MMP-9的表达和直接的抗肿瘤作用有关。 相似文献
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目的：探讨基质金属蛋白酶2、9(MMP-2、MMP-9)在鼻咽癌及其淋巴结转移灶组织中的表达、意义及与EB病毒潜伏膜蛋白1(LMPl)的相关关系。方法：应用免疫组化(SP法)检测LMPl和MMP-2、MMP-9在人鼻咽粘膜慢性炎(30例)、鼻咽癌(30例)和鼻咽癌颈部淋巴结转移灶(24例)组织中的表达。结果：鼻咽癌和鼻咽癌颈部淋巴结转移灶组织中LMPl和MMP-2、MMP-9的阳性率明显高于鼻咽粘膜慢性炎。在鼻咽癌及鼻咽癌颈部淋巴结转移灶标本中还发现癌巢周边的成纤维细胞、癌周浸润的单核细胞、淋巴细胞以及血管内皮细胞中也有MMP-2和MMP-9的表达。Spearman相关分析显示，在鼻咽癌组织中LMPl与MMP-2、MMP-9的表达无相关性；而在鼻咽癌颈部淋巴结转移灶组织中，LMPl的表达与MMP-2、MMP-9的表达呈中度正相关。结论：MMP-2、MMP-9在鼻咽癌细胞突破基底膜向外扩散及转移中起到重要作用；在鼻咽癌淋巴结转移灶中LMPl与MMP-2、MMP-9的表达呈正相关；LMPl可能参与鼻咽部疾病的恶性转化和癌细胞的浸润转移。 相似文献
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目的：探讨基质金属蛋白酶—2、—9(MMP—2、MMP—9)在乳腺良性病变及乳腺癌组织中的表达及意义。方法：应用免疫组化SP法检测10例乳腺良性病变及29例乳腺癌组织中MMP—2和MMP—9的表达。结果：MMP—2和MMP—9在乳腺癌中的表达明显高于乳腺良性组织。且乳腺癌患者中有淋巴结转移组MMP—2、MMP—9的表达明显高于无淋巴结转移组。结论：MMP—2和MMP—9在乳腺癌组织中有高表达且在乳腺癌细胞突破基底膜向外扩散、转移中起着重要作用，两者参与了乳腺癌的转移过程。 相似文献
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Lyapina S Cope G Shevchenko A Serino G Tsuge T Zhou C Wolf DA Wei N Shevchenko A Deshaies RJ 《Science (New York, N.Y.)》2001,292(5520):1382-1385
SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits--including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation. 相似文献
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Schneider H Downey J Smith A Zinselmeyer BH Rush C Brewer JM Wei B Hogg N Garside P Rudd CE 《Science (New York, N.Y.)》2006,313(5795):1972-1975
The coreceptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is pivotal in regulating the threshold of signals during T cell activation, although the underlying mechanism is still not fully understood. Using in vitro migration assays and in vivo two-photon laser scanning microscopy, we showed that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)-induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells. This event led to reduced contact periods between T cells and antigen-presenting cells that in turn decreased cytokine production and proliferation. These results suggest a fundamentally different model of reverse stop signaling, by which CTLA-4 modulates the threshold for T cell activation and protects against autoimmunity. 相似文献
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目的探讨血清基质金属蛋白酶（MMP-2,MMP-9）及T淋巴细胞亚群与肺癌临床类型及临床分期的关系．方法采用ELISA法测定各期肺癌患者血浆中MMP-2和MMP-9的含量,应用流式细胞仪进行外周血中T淋巴细胞的CD3,CD4,CD8,CD4／CD8＋的测定．结果血清MMP-2,MMP-9外周血CD8T淋巴细胞与NSCLC的分型无关,但高于对照组,CD3,CD4低于对照组;随着临床分期的增加,血清MMP-2,MMP-9明显增高,CD3,CD4,CD8,CD4＋／CD8＋低于对照组,具有统计学意义．结论MMP-2,MMP-9联合T淋巴细胞亚群可作为监测肺癌的发生、侵袭和转移更为精确的指标． 相似文献
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目的探讨COX-2,MMP-9和bFGF在大肠癌发生、发展及浸润转移中的作用及相互关系．方法应用免疫组化染色（SP）法检测COX-2,MMP-9和bFGF在66例大肠癌及22例正常大肠组织的表达情况．结果大肠癌组织COX-2,MMP-9和bFGF阳性表达率分别为84．8％,75．8％,65．2％,与正常大肠组织的27．3％,9．1％和4．5％相比有显著性差异（P〈0．01）,COX-2表达与肿瘤组织的浸润深度和淋巴结转移显著相关（P〈0．05）;MMP-9表达与淋巴结转移显著相关（P〈0．05）;bFGF表达与肿瘤组织的浸润深度显著相关（P〈0．05）;Spearman等级相关检验显示,COX-2的表达与MMP-9和bFGF的表达显著相关（P〈0．05,P〈0．01）．结论COX-2,MMP-9和bFGF在大肠癌的发生、发展中发挥着重要作用,COX-2可能通过促进MMP-9和bFGF的表达,从而促进大肠癌的浸润和转移． 相似文献
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Viviani D Charlet A van den Burg E Robinet C Hurni N Abatis M Magara F Stoop R 《Science (New York, N.Y.)》2011,333(6038):104-107
Central amygdala (CeA) projections to hypothalamic and brain stem nuclei regulate the behavioral and physiological expression of fear, but it is unknown whether these different aspects of the fear response can be separately regulated by the CeA. We combined fluorescent retrograde tracing of CeA projections to nuclei that modulate fear-related freezing or cardiovascular responses with in vitro electrophysiological recordings and with in vivo monitoring of related behavioral and physiological parameters. CeA projections emerged from separate neuronal populations with different electrophysiological characteristics and different response properties to oxytocin. In vivo, oxytocin decreased freezing responses in fear-conditioned rats without affecting the cardiovascular response. Thus, neuropeptidergic signaling can modulate the CeA outputs through separate neuronal circuits and thereby individually steer the various aspects of the fear response. 相似文献
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For at least 30 years, matrix metalloproteinases (MMPs) have been heralded as promising targets for cancer therapy on the basis of their massive up-regulation in malignant tissues and their unique ability to degrade all components of the extracellular matrix. Preclinical studies testing the efficacy of MMP suppression in tumor models were so compelling that synthetic metalloproteinase inhibitors (MPIs) were rapidly developed and routed into human clinical trials. The results of these trials have been disappointing. Here we review the studies that brought MPIs into clinical testing and discuss the design and outcome of the trials in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression. The important lessons learned from the MPI experience may be of great value for future studies of MPIs and for cancer drug development in general. 相似文献
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Dubertret B Skourides P Norris DJ Noireaux V Brivanlou AH Libchaber A 《Science (New York, N.Y.)》2002,298(5599):1759-1762
Fluorescent semiconductor nanocrystals (quantum dots) have the potential to revolutionize biological imaging, but their use has been limited by difficulties in obtaining nanocrystals that are biocompatible. To address this problem, we encapsulated individual nanocrystals in phospholipid block-copolymer micelles and demonstrated both in vitro and in vivo imaging. When conjugated to DNA, the nanocrystal-micelles acted as in vitro fluorescent probes to hybridize to specific complementary sequences. Moreover, when injected into Xenopus embryos, the nanocrystal-micelles were stable, nontoxic (<5 x 10(9) nanocrystals per cell), cell autonomous, and slow to photobleach. Nanocrystal fluorescence could be followed to the tadpole stage, allowing lineage-tracing experiments in embryogenesis. 相似文献