Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry最新文献_第9页

Comparative Analysis of Proteins Associated with 26S and 20S Proteasomes Isolated from Rabbit Brain and Liver 兔脑和肝脏中26S和20S蛋白酶体相关蛋白的比较分析

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030040

O. A. Buneeva, A. T. Kopylov, V. G. Zgoda, O. V. Gnedenko, S. A. Kaloshina, M. V. Medvedeva, A. S. Ivanov, A. E. Medvedev

The fractions of 26S and 20S proteasomes have been isolated from the rabbit liver and the brain. According to mass spectrometric (MS) analysis, the 26S proteasome fractions from these organs contained catalytic and regulatory subunits characteristic of the proteasome core and regulatory subunits. The 20S fractions of brain and liver proteasomes contained only catalytic proteasome subunits. In addition to the proteasome subunits, the isolated fractions contained components of the ubiquitin-proteasome system, ubiquitinated proteins, enzymes involved in various metabolic processes, cytoskeletal components, signaling, regulatory, and protective proteins, as well as proteins regulating gene expression, cell division, and differentiation. The abundance of a number of proteasome-associated proteins was comparable or exceeded the abundance of intrinsic proteasome components. About a third of the proteins common to all studied fractions (26S and 20S of brain and liver proteasomes) belong to the group of multifunctional proteins. Selective biosensor validation confirmed the affinity binding of proteins (aldolase, phosphoglycerate kinase) identified during MS analysis to the brain 20S proteasome. Comparison of the subproteomes of the 26S and 20S brain proteasomes showed that removal of components of the regulatory (19S) subparticles caused almost two-fold increase in the total number of individual proteins associated with the core part of the proteasome (20S). In the liver, the number of proteins associated with the core part of the proteasome remained basically unchanged after the removal of the components of the regulatory (19S) subparticles. This indicates that in the brain and, possibly, in other organs, proteins of the regulatory (19S) subunit play an important role in the formation of the proteasome interactome.

从家兔肝脏和脑组织中分离到26S和20S蛋白酶体。质谱分析表明，这些器官的26S蛋白酶体组分含有催化和调节亚基，这些亚基具有蛋白酶体核心和调节亚基的特征。脑和肝蛋白酶体的20S部分仅含有催化蛋白酶体亚基。除了蛋白酶体亚基外，分离的组分还含有泛素-蛋白酶体系统的组分、泛素化蛋白、参与各种代谢过程的酶、细胞骨架组分、信号传导、调节和保护蛋白，以及调节基因表达、细胞分裂和分化的蛋白。许多蛋白酶体相关蛋白的丰度与内在蛋白酶体成分的丰度相当或超过。所研究的所有部分(脑和肝蛋白酶体的26S和20S)共有的蛋白质中约有三分之一属于多功能蛋白质组。选择性生物传感器验证证实了在质谱分析中鉴定的蛋白(醛缩酶、磷酸甘油酸激酶)与脑20S蛋白酶体的亲和力结合。对26S和20S脑蛋白酶体亚蛋白质组的比较表明，去除调节(19S)亚颗粒的成分导致与蛋白酶体核心部分(20S)相关的单个蛋白质总数增加了近两倍。在肝脏中，去除调节(19S)亚颗粒的成分后，与蛋白酶体核心部分相关的蛋白质数量基本保持不变。这表明，在大脑中，也可能在其他器官中，调节(19S)亚基的蛋白质在蛋白酶体相互作用组的形成中起着重要作用。

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引用次数: 2

Lipidomic Markers of Tumor Progress in Breast Cancer Patients 乳腺癌患者肿瘤进展的脂质组学标志物

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030118

A. O. Tokareva, N. L. Starodubtseva, V. V. Chagovets, V. V. Rodionov, V. V. Kometova, K. S. Chingin, V. E. Frankevich

Abstract—

Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles were investigated for their association with the following clinical and morphological characteristics: tumor size, cancer stage, multifocality, tumor grade, number of lymph node metastases, Nottingham prognostic index, total malignancy score, and the level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of the lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 lipid features belonged to phosphatidylcholines. In the lipid profile of tumor microenvironment tissue, 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 lipid features belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, 4 lipid features belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with the tumor size, the cancer stage, the tumor grade, the number of axillary metastases, and the Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.

摘要研究肿瘤进展机制及其对肿瘤细胞和肿瘤微环境细胞代谢的影响是肿瘤靶向治疗药物开发的重要内容。在本研究中，我们研究了肿瘤组织和边缘组织脂质谱的变化与以下临床和形态学特征的关系:肿瘤大小、肿瘤分期、多灶性、肿瘤分级、淋巴结转移数量、诺丁汉预后指数、恶性肿瘤总评分和Ki67蛋白水平。脂质分析采用反相质谱法对脂质组织提取物进行分析，并通过特征片段进行脂质鉴定。在肿瘤组织脂质谱中选取了13种特征脂质。它们的水平与至少5个临床和形态学特征显著相关。13个脂质特征中有8个属于磷脂酰胆碱。在肿瘤微环境组织的脂质谱中，选取了13个脂质特征。它们的水平与至少5个临床和形态学特征显著相关。13个脂质特征中有4个属于氧化脂质，4个属于鞘磷脂，4个属于磷脂酰乙醇胺。肿瘤微环境组织脂质谱与肿瘤大小、肿瘤分期、肿瘤分级、腋窝转移数、诺丁汉预后指数相关。肿瘤组织脂质谱与肿瘤大小、肿瘤分级、总恶性评分和腋窝转移数相关。

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引用次数: 1

Population Rearrangement of B Lymphocytes Expressing Chemokine Receptors in Patients with Chronic Obstructive Pulmonary Disease 慢性阻塞性肺疾病患者表达趋化因子受体的B淋巴细胞群体重排

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030064

A. G. Kadushkin, A. D. Tahanovich, L. V. Movchan, M. M. Zafranskaya, V. V. Dziadzichkina, T. V. Shman

Abstract—

To date, there are no drugs that can prevent progressive destruction of lung tissue and small airway fibrosis in patients with chronic obstructive pulmonary disease (COPD). Therefore, molecular mechanisms of this disease are being studied. The aim of this study was to determine the chemokine receptor expression pattern of B lymphocytes from peripheral blood and airways of COPD patients. Peripheral blood was collected from 51 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers. Seven smokers with COPD and 7 healthy smokers were recruited to undergo bronchoscopy with bronchoalveolar lavage (BAL). The expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 on the surface of blood and BAL B lymphocytes was determined by flow cytometry. It was found that the percentage of blood B lymphocytes expressing chemokine receptors CCR5 and CXCR3 was higher in smokers with COPD compared with healthy smokers and healthy non-smokers. The percentage of CD27⁺ B cells expressing receptors CCR5 and CXCR3 exceeded the proportion of CD27^– B lymphocytes expressing these receptors in peripheral blood of patients with COPD and healthy controls. In smoking patients with COPD, the percentage of BAL B cells expressing receptors CCR5 and CXCR3 was also increased compared with healthy smokers. There were no differences in the percentage of B lymphocytes expressing receptors CXCR4, CXCR5, CCR6, and CCR7 in both peripheral blood and BAL between smokers with COPD and healthy smokers. A greater percentage of CD27^– B lymphocytes than CD27⁺ B cells expressed receptors CXCR4, CXCR5, CCR6, and CCR7 in peripheral blood of smokers with COPD and healthy controls. The results of this study indicate a modification in the chemokine receptor profile of B lymphocytes in COPD.

迄今为止，还没有药物可以预防慢性阻塞性肺疾病(COPD)患者肺组织的进行性破坏和小气道纤维化。因此，该疾病的分子机制正在研究中。本研究的目的是测定COPD患者外周血和气道B淋巴细胞趋化因子受体的表达模式。采集了51例COPD吸烟者、21例健康吸烟者和20例健康非吸烟者的外周血。7名慢性阻塞性肺病吸烟者和7名健康吸烟者接受支气管镜检查和支气管肺泡灌洗(BAL)。流式细胞术检测趋化因子受体CCR5、CCR6、CCR7、CXCR3、CXCR4、CXCR5在血液和BAL B淋巴细胞表面的表达。结果发现，COPD吸烟者血液中表达趋化因子受体CCR5和CXCR3的B淋巴细胞比例高于健康吸烟者和健康非吸烟者。COPD患者和健康对照组外周血中表达受体CCR5和CXCR3的CD27+ B细胞的比例超过表达这些受体的CD27 - B淋巴细胞的比例。在吸烟的COPD患者中，与健康吸烟者相比，表达受体CCR5和CXCR3的BAL B细胞百分比也有所增加。慢性阻塞性肺病吸烟者与健康吸烟者外周血和BAL中表达受体CXCR4、CXCR5、CCR6和CCR7的B淋巴细胞百分比无差异。COPD患者和健康对照者外周血中CD27 - B淋巴细胞表达受体CXCR4、CXCR5、CCR6和CCR7的比例高于CD27+ B细胞。本研究结果表明慢性阻塞性肺病患者B淋巴细胞趋化因子受体谱发生改变。

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引用次数: 2

Expression Levels and Activity of Rat Liver Lactate Dehydrogenase Isoenzymes in Alloxan Diabetes 四氧嘧啶型糖尿病大鼠肝脏乳酸脱氢酶同工酶的表达水平和活性

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030052

A. T. Eprintsev, I. R. Bondareva, N. V. Selivanova

Abstract—

A significant decrease in the activity of liver lactate dehydrogenase (LDH, EC 1.1.1.27) associated with a decrease in the expression of the corresponding genes was found in rats with alloxan-induced diabetes. The decrease in the LDH activity was due to the cytoplasmic isoform of this enzyme. It was found that the level of ldha and ldhb gene transcripts in the liver of healthy rats was higher than in animals with alloxan diabetes. The ldha gene expression demonstrated almost 9-fold decrease, while a decrease in the ldhb gene expression was less pronounced (just 1.25-fold). Our data indicate an important role of LDH in the adaptive response of cellular metabolism in the development of type I diabetes mellitus.

摘要:四氧嘧啶诱导的糖尿病大鼠肝脏乳酸脱氢酶(LDH, EC 1.1.1.27)活性显著降低，相关基因表达降低。LDH活性的降低是由于这种酶的细胞质异构体。结果发现，健康大鼠肝脏中ldha和ldhb基因转录本水平高于四氧嘧啶糖尿病动物。ldha基因表达几乎下降了9倍，而ldhb基因表达的下降则不那么明显(仅为1.25倍)。我们的数据表明LDH在I型糖尿病发生过程中细胞代谢的适应性反应中起重要作用。

引用次数: 0

Screening Analysis of Proteolytic Enzymes and Their Inhibitors in the Leaflets of Epoxy-Treated Bioprosthetic Heart Valves Explanted due to Dysfunction 环氧树脂处理的功能障碍外植心脏瓣膜小叶蛋白水解酶及其抑制剂的筛选分析

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030076

A. E. Kostyunin, T. V. Glushkova, D. K. Shishkova, V. E. Markova, E. A. Ovcharenko

Abstract—

Bioprosthetic heart valves (BHVs) have lower thrombogenicity rates and excellent hemodynamic parameters similar to native valves. However, the lifespan of these medical devices is limited to 15 years due to the structural valve degeneration (SVD). One of the mechanisms underlying functional impairment and calcification of BHVs includes proteolytic degradation of biomaterials. However, proteases found in xenogeneic tissue of BHVs remain poorly studied. In this study using the dot blot assay, we have performed a screening analysis of proteolytic enzymes and their inhibitors in the leaflets of five BHVs explanted due to dysfunction. Five aortic valves (AVs) explanted due to calcific aortic valve disease were used as a comparison group. The results of the study have demonstrated the presence of at least 17 proteases and 19 of their inhibitors in BHVs. In the AVs 20 proteases and 21 of their inhibitors were identified. Small quantitative differences were found between proteomic profiles of BHVs and AVs. Matrix metalloproteinases (MMPs) were expressed in BHVs and AVs at comparable levels, but the level of tissue inhibitors of metalloproteinases-1/-2 and reversion-inducing-cysteine-rich protein with Kazal motifs in implant tissues was lower than in native valves. This suggests that excessive activity of MMPs cannot be counterbalanced by their specific inhibitors in BHVs and therefore MMPs initiate the process of degeneration. Moreover, the detection of a wide range of proteolytic enzymes and their inhibitors in the degenerated BHVs suggests the existence of several pathophysiological pathways that can lead to SVD.

生物人工心脏瓣膜(bhv)具有较低的血栓形成率和良好的血流动力学参数，与天然瓣膜相似。然而，由于结构性瓣膜退行性变(SVD)，这些医疗器械的使用寿命被限制在15年。bhv功能损伤和钙化的机制之一包括生物材料的蛋白水解降解。然而，在bhv异种组织中发现的蛋白酶研究仍然很少。在这项研究中，我们使用点印迹法对5个因功能障碍而外植的bhv小叶中的蛋白水解酶及其抑制剂进行了筛选分析。以5例因钙化性主动脉瓣病变而切除的主动脉瓣(AVs)为对照组。研究结果表明，bhv中存在至少17种蛋白酶和19种蛋白酶抑制剂。在av中鉴定出20种蛋白酶和21种蛋白酶抑制剂。在bhv和av的蛋白质组学谱之间发现了微小的数量差异。基质金属蛋白酶(MMPs)在bhv和AVs中的表达水平相当，但金属蛋白酶组织抑制剂-1/ 2和具有Kazal基序的逆转诱导半胱氨酸富蛋白在植入组织中的表达水平低于天然瓣膜。这表明MMPs的过度活性不能被bhv中的特定抑制剂抵消，因此MMPs启动了变性过程。此外，在退行性bhv中检测到广泛的蛋白水解酶及其抑制剂，表明存在几种可导致SVD的病理生理途径。

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引用次数: 1

Influence of N-Alkynylaminosteroids on Mitochondrial Functioning and Autophagy in Glioma Cells n -炔酰氨基类固醇对胶质瘤细胞线粒体功能和自噬的影响

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S199075082203009X

J. U. Panada, V. A. Klopava, T. A. Kulahava, Y. V. Faletrov, N. S. Frolova, S. V. Koran, E. G. Fomina, V. M. Shkumatov

Abstract—

The effect of the synthesized N-alkynyl-17-aminosteroids and N-alkynyl-20-aminosteroids (based on dehydroepiandrosterone and pregnenolone, respectively) on C6 rat glioma cell functions has been investigated. At 10 μM, the compounds had an insignificant effect on C6 glioma mitochondrial membrane potential, but increased cell autophagy by 70–90%; this effect was comparable to the known autophagy inducer dexamethasone. Docking simulations predict a potential high-affinity interaction between N-alkynylaminosteroids and Keap1 and the Hedgehog pathway protein, Smoothened, which are involved in autophagy regulation. The possible mechanisms of observed processes are discussed.

摘要:本文研究了合成的n -炔基17-氨基类固醇和n -炔基20-氨基类固醇(分别以脱氢表雄酮和孕烯醇酮为基础)对C6大鼠胶质瘤细胞功能的影响。在10 μM时，化合物对C6胶质瘤线粒体膜电位影响不显著，但使细胞自噬增加70-90%;这种效果与已知的自噬诱导剂地塞米松相当。对接模拟预测了n -炔酰氨基类固醇与Keap1和Hedgehog通路蛋白Smoothened之间潜在的高亲和相互作用，它们参与自噬调节。讨论了观测过程的可能机制。

引用次数: 1

Increased Suppressor Activity of Ex Vivo Transformed Regulatory T Cells in Comparison with Unstimulated Cells of the Same Donor 体外转化调节性T细胞与同一供体未刺激细胞相比抑制活性增加

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030039

V. G. Blinova, Y. A. Gladilina, D. D. Eliseeva, T. A. Lobaeva, D. D. Zhdanov

Abstract—

Regulatory T cells CD4⁺CD25⁺FoxP3⁺СD127^low (Tregs) play a key role in the maintenance of tolerance to autoantigens, inhibit the function of effector T and B lymphocytes, and provide a balance between effector and regulatory arms of immunity. Patients with autoimmune diseases are characterized by decreased Treg numbers and impaired suppressive activity. Replacement therapy with autologous Tregs transformed ex vivo could restore the destroyed balance of the immune system. We developed a method for the cultivation of Treg precursor cells. Using this method, we were able to grow up to 300−400 million Treg cells from 50 mL of peripheral blood during a week. In this study, we demonstrated that 90−95% of ex vivo-transformed Tregs had the phenotype CD4⁺CD25⁺FoxP3⁺СD127^low and increased the transcription of the FoxP3 and Helios genes. Ex vivo-transformed Tregs were characterized by increased demethylation of the FoxP3 promoter and activation of the proliferation gene markers cyclin B1, Ki67 and LGALS 1. Ex vivo-transformed Tregs had increased suppressive activity, and up to 80–90% of these cells secreted the cytokines TNFα and IFNγ. Our data suggest that ex vivo-transformed autologous Tregs have genetic, immunophenotypic and functional characteristics of regulatory T cells. In the future, they can be used for adoptive immunotherapy of autoimmune diseases and inhibition of transplantation immunity.

调节性T细胞CD4+CD25+FoxP3+СD127low (Tregs)在维持对自身抗原的耐受性，抑制效应T和B淋巴细胞的功能，并在免疫的效应和调节臂之间提供平衡方面发挥关键作用。自身免疫性疾病患者的特点是Treg数量减少和抑制活性受损。体外转化的自体Tregs替代疗法可以恢复被破坏的免疫系统平衡。我们开发了一种培养Treg前体细胞的方法。使用这种方法，我们能够在一周内从50 mL的外周血中培养出3 - 4亿个Treg细胞。在这项研究中，我们证明了90 - 95%的离体转化treg具有CD4+CD25+FoxP3+СD127low表型，并且增加了FoxP3和Helios基因的转录。体外转化Tregs的特征是FoxP3启动子的去甲基化增加，增殖基因标记细胞周期蛋白B1、Ki67和LGALS 1的激活。体外转化的Tregs具有增强的抑制活性，高达80-90%的这些细胞分泌细胞因子TNFα和IFNγ。我们的数据表明体外转化的自体Tregs具有调节性T细胞的遗传、免疫表型和功能特征。在未来，它们可用于自身免疫性疾病的过继免疫治疗和移植免疫抑制。

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引用次数: 0

The Integrin α3β1 Signaling in the Regulation of the SK-Mel-147 Melanoma Cell Senescence 整合素α3β1信号在SK-Mel-147黑色素瘤细胞衰老中的调控作用

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-08-15 DOI: 10.1134/S1990750822030088

G. E. Morozevich, N. I. Kozlova, N. M. Gevorkian, A. E. Berman

Abstract—

Using a model of the human SK-Mel-147 melanoma cell line, it was shown that blocking the expression of integrin α3β1 by transduction of cells with α3-specific shRNA did not affect their proliferation, but sharply increased the proportion of SA-β-Gal-positive cells, a phenotypic feature of cell senescence. These changes were accompanied by a significant increase in the activity of the Akt and mTOR protein kinases and the expression of p53 and p21 oncosupressors. The pharmacological inhibition of mTORC1 reduced the number SA-β-Gal-positive cells in the SK-Mel-147 cell population depleted of α3β1. Based on our recent data on a non-canonical function of Akt isoforms in the regulation of SK-Mel-147 cell senescence caused by α2β1 receptor deficiency, we have investigated the role of Akt isoforms in senescence induced by the α3β1 knockdown. It appeared that in the cell population with downregulated α3β1, inhibition of Akt1 reduced the number SA-β-Gal positive cells to the level of control cell population, while inhibition of Akt2 had no visible effect. Our results demonstrate that: (i) the laminin-specific integrin α3β1, like the collagen-specific receptor α2β1, is involved in tumor cell protection from senescence; (ii) senescence induced by α3β1 suppression is based on a signaling mechanism employing a non-canonical function of the Akt1 isoform.

摘要利用人SK-Mel-147黑色素瘤细胞系模型，发现通过α3特异性shRNA转导细胞阻断整合素α3β1的表达不影响其增殖，但显著增加了SA-β- gal阳性细胞的比例，这是细胞衰老的表型特征。这些变化伴随着Akt和mTOR蛋白激酶活性以及p53和p21肿瘤抑制因子表达的显著增加。mTORC1的药理抑制减少了α3β1缺失的SK-Mel-147细胞群中SA-β- gal阳性细胞的数量。基于我们最近关于Akt亚型在α2β1受体缺失引起的SK-Mel-147细胞衰老调控中的非规范功能的数据，我们研究了Akt亚型在α3β1敲低诱导的衰老中的作用。可见，在α3β1下调的细胞群中，抑制Akt1使SA-β-Gal阳性细胞数量减少到对照细胞群的水平，而抑制Akt2则无明显作用。结果表明:(1)层粘连蛋白特异性整合素α3β1与胶原特异性受体α2β1一样，参与肿瘤细胞的抗衰老作用;(ii) α3β1抑制诱导的衰老是基于Akt1亚型非规范功能的信号机制。

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引用次数: 0

Cysteine Cathepsins: Structure, Physiological Functions, and the Role in Carcinogenesis 半胱氨酸组织蛋白酶:结构、生理功能和在癌变中的作用

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020056

T. A. Gureeva, O. S. Timoshenko, E. V. Kugaevskaya, N. I. Solovyova

Abstract—

Cysteine cathepsins (Cts) also known as thiol proteinases belong to the superfamily of cysteine proteinases. Most Cts are endopeptidases; some of them exhibit exopeptidase activity. All Cts are synthesized as zymogens and activation of most of them occurs autocatalytically. Ct activity depends on pH and it is regulated by endogenous inhibitors. Although the major role of Cts consists in lysosomal degradation of cell proteins these enzymes are also detected in the nucleus, cytoplasm, plasma membrane, and in the extracellular medium. The latter is especially important in the case of certain pathological including cancer. Extracellular Cts not only hydrolyze extracellular matrix (ECM) proteins, but also contribute to ECM remodeling via specific processing of various proteins including cytokines, chemokines, cell adhesion molecules. Normally, expression and activity of Cts are very low and these enzymes are mainly detected inside cells. In cancer, the expression and activity of Cts sharply increase both in cell lysosomes and in the intercellular space and this promotes neoplastic transformation, invasion, metastasis and leads to further tumor progression. It has been shown that Cts expression depends on the cells type, and therefore, their role in the tumor development differs in dependence of their cellular origin. However, the mechanism of Cts action is not limited only by their proteolytic degradation of ECM proteins. Cts play an important role in processing of proteins involved in oncogenic cell signaling. For example, Cts participation in processing of growth factors is mediated through receptor tyrosine kinases (RTK) and various signaling mitogen-activated protein kinases (MAPK), which are involved in regulation of such cell processes as gene transcription, apoptosis, proliferation, and cell migration capacity. In addition, Cts also promote the epithelial-mesenchymal transition (EMT) by activating TGF-β signaling, which is considered as one of the key signaling pathways in this process.

摘要:半胱氨酸组织蛋白酶(Cts)也被称为巯基蛋白酶，属于半胱氨酸蛋白酶超家族。大多数ct是内肽酶;其中一些具有外肽酶活性。所有的ct都是作为酶原合成的，它们中的大多数都是自催化激活的。Ct活性取决于pH值，并受内源性抑制剂调节。虽然Cts的主要作用在于细胞蛋白的溶酶体降解，但这些酶在细胞核、细胞质、质膜和细胞外介质中也被检测到。后者在某些病理包括癌症的情况下尤为重要。细胞外Cts不仅可以水解细胞外基质(ECM)蛋白，还可以通过对细胞因子、趋化因子、细胞粘附分子等多种蛋白的特异性加工，促进细胞外基质的重塑。正常情况下，Cts的表达和活性都很低，这些酶主要在细胞内检测到。在癌症中，细胞溶酶体和细胞间隙中Cts的表达和活性急剧增加，促进肿瘤转化、侵袭、转移，导致肿瘤进一步进展。研究表明，Cts的表达依赖于细胞类型，因此，它们在肿瘤发展中的作用取决于它们的细胞来源。然而，Cts的作用机制不仅限于它们对ECM蛋白的蛋白水解降解。ct在肿瘤细胞信号传导过程中发挥重要作用。例如，Cts参与生长因子的加工是通过受体酪氨酸激酶(RTK)和各种信号分裂原活化蛋白激酶(MAPK)介导的，它们参与基因转录、凋亡、增殖和细胞迁移能力等细胞过程的调节。此外，Cts还通过激活TGF-β信号通路促进上皮-间质转化(epithelial-mesenchymal transition, EMT)， TGF-β被认为是这一过程中的关键信号通路之一。

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引用次数: 0

Atmospheric Reactive Oxygen Species and Some Aspects of the Antiviral Protection at the Respiratory Epithelium 大气活性氧及其在呼吸道上皮细胞抗病毒保护中的作用

IF 0.6 Q4 Biochemistry, Genetics and Molecular Biology

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry

Pub Date : 2022-05-17 DOI: 10.1134/S1990750822020068

V. V. Salmin, A. V. Morgun, R. Ya. Olovyannikova, V. A. Kutyakov, E. V. Lychkovskaya, E. B. Brusina, A. B. Salmina

Abstract—

The review summarizes literature data on molecular and biochemical mechanisms of nonspecific protection of respiratory epithelium. The special attention is paid to comprehensive analysis of up-to-date data on the activity of the lactoperoxidase system expressed on the surface of the respiratory epithelium which provides the generation of hypothiocyanate and hypoiodite in the presence of locally produced or inhaled hydrogen peroxide. Molecular mechanisms of production of active compounds with antiviral and antibacterial effects, expression profiles of enzymes, transporters and ion channels involved in the generation of hypothiocyanite and hypoiodite in the mucous membrane of the respiratory system in physiological and pathological conditions (inflammation) are discussed. A hypothesis about the effect of atmospheric air composition on the efficiency of hypothiocyanate and hypoiodite generation in the respiratory epithelium in the context of its antibacterial and antiviral protection is presented. The causes and consequences of insufficiency of the lactoperoxidase system caused by the action of atmospheric factors are discussed in the context of controlling the sensitivity of the epithelium to the action of bacterial agents and viruses. Good evidence exists that restoration of the lactoperoxidase system activity can be achieved by application of pharmacological agents aimed to compensate for the deficit of halides in tissues, and by the control of chemical composition of the inhaled air.

摘要综述了呼吸上皮非特异性保护的分子生化机制的文献资料。特别关注的是对呼吸上皮表面表达的乳过氧化物酶系统活性的最新数据的综合分析，该系统在当地产生或吸入过氧化氢的情况下产生次硫氰酸盐和次碘酸盐。本文讨论了具有抗病毒和抗菌作用的活性化合物的分子机制，以及在生理和病理条件(炎症)下呼吸系统粘膜中参与次硫氰酸盐和次碘酸盐生成的酶、转运体和离子通道的表达谱。提出了一种关于大气成分对呼吸上皮中次硫氰酸酯和次碘酸酯生成效率的影响的假设，其具有抗菌和抗病毒保护作用。在控制上皮对细菌和病毒的敏感性的背景下，讨论了由大气因素的作用引起的乳过氧化物酶系统功能不足的原因和后果。有充分的证据表明，乳酸过氧化物酶系统活性的恢复可以通过应用药物来弥补组织中卤化物的缺陷，并通过控制吸入空气的化学成分来实现。

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引用次数: 0