Cell Pathology最新文献_第2页

Prion disease and endoplasmic reticulum stress pathway correlations and treatment pursuits 朊病毒疾病与内质网应激途径的相关性及治疗追求

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Cell Pathology Pub Date : 2017-08-28 DOI: 10.1515/ersc-2017-0003

Tarah Satterfield, J. Pritchett, Sarah Cruz, Kyeorda Kemp

{"title":"Prion disease and endoplasmic reticulum stress pathway correlations and treatment pursuits","authors":"Tarah Satterfield, J. Pritchett, Sarah Cruz, Kyeorda Kemp","doi":"10.1515/ersc-2017-0003","DOIUrl":"https://doi.org/10.1515/ersc-2017-0003","url":null,"abstract":"Abstract Background: Transmissible spongiform encephalopathies are a collection of rare neurodegenerative disorders characterized by loss of neuronal cells, astrocytosis, and plaque formation. The causative agent of these diseases is thought to be abnormally folded prions and is characterized by a conformational change from normal, cellular prion protein (PrPc) to the abnormal form (PrPTSE). Although, there is evidence that normal prion protein can contribute to these disorders. The unfolded protein response, a conserved series of pathways involved in resolving stress associated with unfolded protein accumulation in the Endoplasmic Reticulum (ER), has been shown to play a role in regulating the development of prion diseases. Methods: This review chose papers based on their relevance to current studies involved in prion protein synthesis and transformation, identifies various links between prion diseases and ER stress, and reports on current and potential treatments as they relate to ER stress and prion diseases. Conclusion: For the advancement of prion disease treatment, it is important to understand the mechanisms involved in prion formation, and ER stress is implicated in prion disease progression. Therefore, targeting the ER or pathways involved in response to stress in the ER may help us treat prion diseases.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"1 1","pages":"27 - 36"},"PeriodicalIF":0.7,"publicationDate":"2017-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83537134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

ER stress in neurodegenerative disease: from disease mechanisms to therapeutic interventions 神经退行性疾病中的内质网应激:从发病机制到治疗干预

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Cell Pathology Pub Date : 2017-04-25 DOI: 10.1515/ersc-2017-0002

Felipe Cabral-Miranda, C. Hetz

引用次数: 8

Inhibition of IRE1 signaling affects expression of a subset genes encoding for TNF-related factors and receptors and modifies their hypoxic regulation in U87 glioma cells IRE1信号的抑制影响编码tnf相关因子和受体的亚基因的表达，并改变其在U87胶质瘤细胞中的缺氧调节

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Cell Pathology Pub Date : 2016-01-01 DOI: 10.1515/ersc-2016-0001

O. Minchenko, I. V. Kryvdiuk, D. Minchenko, O. O. Riabovol, O. V. Halkin

{"title":"Inhibition of IRE1 signaling affects expression of a subset genes encoding for TNF-related factors and receptors and modifies their hypoxic regulation in U87 glioma cells","authors":"O. Minchenko, I. V. Kryvdiuk, D. Minchenko, O. O. Riabovol, O. V. Halkin","doi":"10.1515/ersc-2016-0001","DOIUrl":"https://doi.org/10.1515/ersc-2016-0001","url":null,"abstract":"Abstract Inhibition of IRE1 (inositol requiring enzyme-1), the major signaling pathway of endoplasmic reticulum stress, significantly decreases tumor growth and proliferation of glioma cells. To elucidate the role of IRE1- mediated glioma growth, we studied the expression of a subset genes encoding for TNF (tumor necrosis factor)- related factors and receptors and their hypoxic regulation in U87 glioma cells overexpressing dominant-negative IRE1 (dnIRE1). We demonstrated that the expression of TNFAIP1, TNFRSF10D, TNFRSF21, TNFRSF11B, TNFSF7, and LITAF genes is increased in glioma cells with modified IRE1; however, TNFRSF10B, TRADD, and TNFAIP3 is down-regulated in these cells as compared to their control counterparts. We did not find TNFRSF1A gene expression to change significantly under this experimental condition. In control glioma cells, hypoxia leads to the up-regulated expression of TNFAIP1, TNFAIP3, TRADD, and TNFRSF10D genes and the concomitant down-regulation of TNFRSF21, TNFRSF11B, and LITAF genes; while, TNFRSF10B and TNFRSF1A genes are resistant to hypoxic treatment. However, inhibition of IRE1 modifies the hypoxic regulation of LITAF, TNFRSF21, TNFRSF11B, and TRADD genes and introduces hypoxia-induced sensitivity to TNFRSF10B, TNFRSF1A, and TNFSF7 gene expressions. Furthermore, knockdown by siRNA of TNFRSF21 mRNA modifies the hypoxic effect on the IRE1-dependent rate of proliferation and cell death in U87 glioma cells. The present study demonstrates that fine-tuned manipulation of the expression of TNF-related factors and receptors directly relating to cell death and proliferation, is mediated by an effector of endoplasmic reticulum stress, IRE1, as well as by hypoxia in a gene-specific manner. Thus, inhibition of the kinase and endoribonuclease activities of IRE1 correlates with deregulation of TNF-related factors and receptors in a manner that is gene specific and thus slows tumor growth.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"16 1","pages":"1 - 15"},"PeriodicalIF":0.7,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75427913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

IRE-1α regulates expression of ubiquitin specific peptidases during hypoxic response in U87 glioma cells IRE-1α调控U87胶质瘤细胞缺氧反应中泛素特异性肽酶的表达

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Cell Pathology Pub Date : 2016-01-01 DOI: 10.1515/ersc-2016-0003

O. Minchenko, D. O. Tsymbal, D. Minchenko, O. O. Riabovol, O. V. Halkin, O. Ratushna

{"title":"IRE-1α regulates expression of ubiquitin specific peptidases during hypoxic response in U87 glioma cells","authors":"O. Minchenko, D. O. Tsymbal, D. Minchenko, O. O. Riabovol, O. V. Halkin, O. Ratushna","doi":"10.1515/ersc-2016-0003","DOIUrl":"https://doi.org/10.1515/ersc-2016-0003","url":null,"abstract":"Abstract IRE-1α (inositol requiring enzyme-1α), the most evolutionarily conserved of the endoplasmic reticulum stress signaling pathways, is highly implicated in sustaining the proliferation of glioma cells and subsequent tumor growth, which is decreased by the inhibition of IRE-1α. To explore the IRE-1α mediated regulation of ubiquitin system in glioma cells, the expression of a subset of ubiquitin specific peptidases (USP) and of ubiquitin activating enzyme E1-like protein/autophagy related 7 (GSA7/ATG7) genes was studied, during hypoxic stress in wild type and U87 glioma cells with inhibited IRE-1α. Hypoxic treatment of wild type glioma cells leads to the up-regulation of USP25 and the concomitant downregulation of USP1, USP10, USP14, and GSA7 genes. USP4 and USP22 genes expression did not significantly change with hypoxic treatment. Inhibition of IRE-1α activity led to up-regulation of USP1, USP4, USP10, USP22, and USP25, while USP14 and GSA7 genes were down-regulated. Therefore, IRE-1α activity modifies substrate-targeting specificity to proteasome during hypoxic stress, which in turn can affect cell survival. Inhibition of IRE-1α correlates directly with deregulation of ubiquitin specific peptidases and GSA7 in a fashion that ultimately slows tumor growth.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"93 1","pages":"50 - 62"},"PeriodicalIF":0.7,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76457352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

The role of Endoplasmic Reticulum (ER) stress in pulmonary fibrosis 内质网应激在肺纤维化中的作用

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Cell Pathology Pub Date : 2016-01-01 DOI: 10.1515/ersc-2016-0002

M. Korfei, C. Ruppert, Benjamin Loeh, P. Mahavadi, A. Guenther

{"title":"The role of Endoplasmic Reticulum (ER) stress in pulmonary fibrosis","authors":"M. Korfei, C. Ruppert, Benjamin Loeh, P. Mahavadi, A. Guenther","doi":"10.1515/ersc-2016-0002","DOIUrl":"https://doi.org/10.1515/ersc-2016-0002","url":null,"abstract":"Abstract The activation of Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) was first observed in patients with familial interstitial pneumonia (FIP) carrying mutations in the C-terminal BRICHOS domain of surfactant protein C (SFTPC). Here, aggresome formation and severe ER stress was demonstrated in type-II alveolar epithelial cells (AECII), which specifically express this very hydrophobic surfactant protein. In subsequent studies, FIP-patients with mutations in the gene encoding surfactant protein A2 (SFTPA2) were discovered, whose overexpression in epithelial cells in vitro also resulted in significant induction of ER stress. Moreover, prominent ER stress in AECII was also observed in FIP-patients not carrying the SFTPC/SFTPA2 mutations, as well as in patients with the more common sporadic forms of IP. Additionally, cases of adult-onset FIP with mutations in Telomerase genes and other telomereassociated components were reported. These mutations were associated with telomere shortening, which is a potential cause for triggering a persistent DNA damage response and replicative senescence in affected cells. Moreover, shortened telomeres were observed directly in the AECII of FIP-patients, and even sporadic IP cases, in the absence of any gene mutations. Here, we try to figure out the possible origins of ER stress in sporadic IP cases and non-SFTPC/SFTPA2-associated FIP.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"65 1","pages":"16 - 49"},"PeriodicalIF":0.7,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77485622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Endoplasmic reticulum stress response in the roadway for the effects of non-steroidal anti-inflammatory drugs 非甾体抗炎药对巷道内质网应激反应的影响

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Cell Pathology Pub Date : 2015-01-01 DOI: 10.1515/ersc-2015-0001

Fernanda L. B. Mügge, Aristóbolo Mendes Silva

{"title":"Endoplasmic reticulum stress response in the roadway for the effects of non-steroidal anti-inflammatory drugs","authors":"Fernanda L. B. Mügge, Aristóbolo Mendes Silva","doi":"10.1515/ersc-2015-0001","DOIUrl":"https://doi.org/10.1515/ersc-2015-0001","url":null,"abstract":"Abstract Over the past decade, a handful of evidence has been provided that nonsteroidal anti-inflammatory drugs (NSAIDs) display effects on the homeostasis of the endoplasmic reticulum (ER). Their uptake into cells will eventually lead to activation or inhibition of key molecules that mediate ER stress responses, raising not only a growing interest for a pharmacological target in ER stress responses but also important questions how the ER-stress mediated effects induced by NSAIDs could be therapeutically advantageous or not. We review here the toxicity effects and therapeutic applications of NSAIDs involving the three majors ER stress arms namely PERK, IRE1, and ATF6. First, we provide brief introduction on the well-established and characterized downstream events mediated by these ER stress players, followed by presentation of the NSAIDs compounds and mode of action, and finally their effects on ER stress response. NSAIDs present promising drug agents targeting the components of ER stress in different aspects of cancer and other diseases, but a better comprehension of the mechanisms underlying their benefits and harms will certainly pave the road for several diseases’ therapy.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"63 1","pages":"1 - 17"},"PeriodicalIF":0.7,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85638633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease 蛋白质毒性应激在阿尔茨海默病发病机制中血管功能障碍的作用

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Cell Pathology Pub Date : 2015-01-01 DOI: 10.1515/ersc-2015-0005

A. C. Fonseca, R. Resende, S. Cardoso, C. Pereira

{"title":"The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease","authors":"A. C. Fonseca, R. Resende, S. Cardoso, C. Pereira","doi":"10.1515/ersc-2015-0005","DOIUrl":"https://doi.org/10.1515/ersc-2015-0005","url":null,"abstract":"Abstract Alzheimer’s disease (AD) is the principal cause of dementia in the elderly; however, its prevalence is increasing due to the fact that current pharmaceuticals used to manage the symptoms are not capable of preventing, halting, or reversing disease progression. In the last decade, evidence has accumulated to support the hypothesis that a primary cerebral vascular dysfunction initiates the cascade of events that leads to neuronal injury and the subsequent cognitive decline observed in AD. The mechanisms underlying these vascular defects and their relationship with neurodegeneration are still poorly understood however. It is pathologically known that cerebrovascular dysfunctions can induce the deposition of amyloid-β (Aβ), an amyloidogenic and toxic peptide that in turn causes cerebrovascular degeneration. Mammalian cells regulate proteostasis and the functioning of intracellular organelles through diverse mechanisms such as the Unfolded Protein Response, the Ubiquitin-Proteasome System and autophagy; however, when these mechanisms cannot compensate for perturbations in homeostasis, the cell undergoes programmed death via apoptosis. This review summarizes recent studies that together correlate the deregulation of protein quality control pathways with dysfunction of vascular endothelial cells of the brain in AD, thus supporting the hypothesis that it is the vicious, progressive failure of the proteostatic network and endothelial activation that underlies the cerebrovascular changes that symptomize AD.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"2 1","pages":"67 - 81"},"PeriodicalIF":0.7,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79106738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Genesis of ER Stress in Huntington’s Disease 内质网应激在亨廷顿氏病中的成因

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Cell Pathology Pub Date : 2015-01-01 DOI: 10.1515/ersc-2015-0007

M. Shenkman, Hagit Eiger, G. Lederkremer

引用次数: 3

The unfolded protein response, inflammation, oscillators, and disease: a systems biology approach 未折叠蛋白反应、炎症、振荡因子和疾病:系统生物学方法

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Cell Pathology Pub Date : 2015-01-01 DOI: 10.1515/ersc-2015-0003

R. Rangel‐Aldao

引用次数: 3

Inhibition of kinase and endoribonuclease activity of ERN1/IRE1α affects expression of proliferation related genes in U87 glioma cells 抑制ERN1/IRE1α激酶和核糖核酸内切酶活性影响U87胶质瘤细胞增殖相关基因的表达

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Cell Pathology Pub Date : 2015-01-01 DOI: 10.1515/ersc-2015-0002

O. Minchenko, D. O. Tsymbal, D. Minchenko, M. Moenner, O. V. Kovalevska, N. M. Lypova

{"title":"Inhibition of kinase and endoribonuclease activity of ERN1/IRE1α affects expression of proliferation related genes in U87 glioma cells","authors":"O. Minchenko, D. O. Tsymbal, D. Minchenko, M. Moenner, O. V. Kovalevska, N. M. Lypova","doi":"10.1515/ersc-2015-0002","DOIUrl":"https://doi.org/10.1515/ersc-2015-0002","url":null,"abstract":"Abstract Inhibition of ERN1/IRE1α (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme-1α), the major signaling pathway of endoplasmic reticulum stress, significantly decreases tumor growth. We have studied the expression of transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), TBX3 (T-box 3), ATF3 (activating transcription factor 3), FOXF1 (forkhead box F1), and HOXC6 (homeobox C6) in U87 glioma cells overexpressing dominant-negative ERN1/IRE1α defective in endoribonuclease (dnr-ERN1) as well as defective in both kinase and endonuclease (dn-ERN1) activity of ERN1/IRE1α. We have demonstrated that the expression of all studied genes is decreased at the mRNA level in cells with modified ERN1/IRE1α; TBX3, however, is increased in these cells as compared to control glioma cells. Changes in protein levels of E2F8, HOXC6, ATF3, and TBX3 corresponded to changes in mRNAs levels. We also found that two mutated ERN1/IRE1α have differential effects on the expression of studied transcripts. The presence of kinase and endonuclease deficient ERN1/IRE1α in glioma cells had a less profound effect on the expression of E2F8, HOXC6, and TBX3 genes than the blockade of the endoribonuclease activity of ERN1/IRE1α alone. Kinase and endonuclease deficient ERN1/IRE1α suppresses ATF3 and FOXF1 gene expressions, while inhibition of only endoribonuclease of ERN1/IRE1α leads to the up-regulation of these gene transcripts. The present study demonstrates that fine-tuning of the expression of proliferation related genes is regulated by ERN1/IRE1α an effector of endoplasmic reticulum stress. Inhibition of ERN1/IRE1α, especially its endoribonuclease activity, correlates with deregulation of proliferation related genes and thus slower tumor growth.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"80 1","pages":"18 - 29"},"PeriodicalIF":0.7,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91311419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29