International Journal of Cell Biology最新文献

{"title":"Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage.","authors":"Melanie D King,&nbsp;Wittstatt A Whitaker-Lea,&nbsp;James M Campbell,&nbsp;Cargill H Alleyne,&nbsp;Krishnan M Dhandapani","doi":"10.1155/2014/495817","DOIUrl":"https://doi.org/10.1155/2014/495817","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"495817"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/495817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32261092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein misfolding and neurodegenerative diseases.","authors":"Alessio Cardinale,&nbsp;Roberto Chiesa,&nbsp;Michael Sierks","doi":"10.1155/2014/217371","DOIUrl":"https://doi.org/10.1155/2014/217371","url":null,"abstract":"This special issue includes fifteen reviews and two original research articles by leading scientists in the fields of neuropathology, biochemistry, and cell biology, dealing with the role of protein aggregation and prion-like propagation of protein misfolding in neurodegenerative diseases. \u0000 \u0000In the review article “Breaking the code of amyloid-β oligomers,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/950783/, S. E. Lesne outlines the “oligomeric” view of the amyloid hypothesis in Alzheimer's disease (AD), discussing how structurally different amyloid-β (Aβ) oligomers may contribute to the pathogenesis, and the controversial role of the prion protein (PrP) in Aβ toxicity. He stresses the need to thoroughly characterize the oligomeric Aβ assemblies for dissecting the disease mechanisms and designing specific, effective therapies. \u0000 \u0000Tau oligomers may also play an important neurotoxic role in AD. In the research article “Trimeric tau is toxic to human neuronal cells at low nanomolar concentrations,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/260787/, H. Tian et al. show that two nonphosphorylated human recombinant tau splice variants are neurotoxic at low nanomolar concentrations. They provide evidence that trimeric but not monomeric or dimeric tau is responsible for the toxicity. In the review article “The innate immune system in Alzheimer's disease,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/576383/, A. Boutajangout and T. Wisniewski focus on the potential roles of the triggering receptor expressed on myeloid cells 2 protein (TREM2) and Toll-like receptors (TLRs) in AD. They give an overview of TREM2 functions and its involvement in phagocytic and anti-inflammatory pathways. They also review the critical roles of TLR4 and 9 in the innate immune response, the interplay of these pattern recognition receptors, and highlight the importance of microglia-mediated innate immunity in AD pathogenesis. \u0000 \u0000Several articles deal with the cellular processes involved in protein folding and quality control and how their corruption may trigger neurotoxicity. In the review article “Disulfide bonding in neurodegenerative misfolding diseases,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/318319/, M. F. Mossuto discusses the role of disulfide bond formation; in the review article “Role of protein misfolding and proteostasis deficiency in protein misfolding diseases and aging,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/638083/, K. Cuanalo-Contreras et al. review the involvement of the unfolded protein response (UPR), the ubiquitin proteasome system (UPS), autophagy, and aggresome formation in neurodegenerative diseases and aging. In the review article “ER dysfunction and protein folding stress in ALS,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/674751/, S. Matus et al. specificall","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"217371"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/217371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32317208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-nitrosation and ubiquitin-proteasome system interplay in neuromuscular disorders.","authors":"Salvatore Rizza,&nbsp;Costanza Montagna,&nbsp;Giuseppina Di Giacomo,&nbsp;Claudia Cirotti,&nbsp;Giuseppe Filomeni","doi":"10.1155/2014/428764","DOIUrl":"https://doi.org/10.1155/2014/428764","url":null,"abstract":"<p><p>Protein S-nitrosation is deemed as a prototype of posttranslational modifications governing cell signaling. It takes place on specific cysteine residues that covalently incorporate a nitric oxide (NO) moiety to form S-nitrosothiol derivatives and depends on the ratio between NO produced by NO synthases and nitrosothiol removal catalyzed by denitrosating enzymes. A large number of cysteine-containing proteins are found to undergo S-nitrosation and, among them, the enzymes catalyzing ubiquitination, mainly the class of ubiquitin E3 ligases and the 20S component of the proteasome, have been reported to be redox modulated in their activity. In this review we will outline the processes regulating S-nitrosation and try to debate whether and how it affects protein ubiquitination and degradation via the proteasome. In particular, since muscle and neuronal health largely depends on the balance between protein synthesis and breakdown, here we will discuss the impact of S-nitrosation in the efficiency of protein quality control system, providing lines of evidence and speculating about its involvement in the onset and maintenance of neuromuscular dysfunctions. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"428764"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/428764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32174100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-cys peroxiredoxins: emerging hubs determining redox dependency of Mammalian signaling networks.","authors":"Jinah Park,&nbsp;Sunmi Lee,&nbsp;Sanghyuk Lee,&nbsp;Sang Won Kang","doi":"10.1155/2014/715867","DOIUrl":"https://doi.org/10.1155/2014/715867","url":null,"abstract":"<p><p>Mammalian cells have a well-defined set of antioxidant enzymes, which includes superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins. Peroxiredoxins are the most recently identified family of antioxidant enzymes that catalyze the reduction reaction of peroxides, such as H2O2. In particular, typical 2-Cys peroxiredoxins are the featured peroxidase enzymes that receive the electrons from NADPH by coupling with thioredoxin and thioredoxin reductase. These enzymes distribute throughout the cellular compartments and, therefore, are thought to be broad-range antioxidant defenders. However, recent evidence demonstrates that typical 2-Cys peroxiredoxins play key signal regulatory roles in the various signaling networks by interacting with or residing near a specific redox-sensitive molecule. These discoveries help reveal the redox signaling landscape in mammalian cells and may further provide a new paradigm of therapeutic approaches based on redox signaling. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"715867"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/715867","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32212719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of autophagy on cell death modalities.","authors":"Stefan W Ryter, Kenji Mizumura, Augustine M K Choi","doi":"10.1155/2014/502676","DOIUrl":"10.1155/2014/502676","url":null,"abstract":"<p><p>Autophagy represents a homeostatic cellular mechanism for the turnover of organelles and proteins, through a lysosome-dependent degradation pathway. During starvation, autophagy facilitates cell survival through the recycling of metabolic precursors. Additionally, autophagy can modulate other vital processes such as programmed cell death (e.g., apoptosis), inflammation, and adaptive immune mechanisms and thereby influence disease pathogenesis. Selective pathways can target distinct cargoes (e.g., mitochondria and proteins) for autophagic degradation. At present, the causal relationship between autophagy and various forms of regulated or nonregulated cell death remains unclear. Autophagy can occur in association with necrosis-like cell death triggered by caspase inhibition. Autophagy and apoptosis have been shown to be coincident or antagonistic, depending on experimental context, and share cross-talk between signal transduction elements. Autophagy may modulate the outcome of other regulated forms of cell death such as necroptosis. Recent advances suggest that autophagy can dampen inflammatory responses, including inflammasome-dependent caspase-1 activation and maturation of proinflammatory cytokines. Autophagy may also act as regulator of caspase-1 dependent cell death (pyroptosis). Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases in which apoptosis or other forms of regulated cell death may play a cardinal role. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"502676"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32184243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA and functional investigations into the radiosensitivity of four mouse strains.","authors":"Steven B Zhang, David Maguire, Mei Zhang, Yeping Tian, Shanmin Yang, Amy Zhang, Katherine Casey-Sawicki, Deping Han, Jun Ma, Liangjie Yin, Yongson Guo, Xiaohui Wang, Chun Chen, Alexandra Litvinchuk, Zhenhuan Zhang, Steven Swarts, Sadasivan Vidyasagar, Lurong Zhang, Paul Okunieff","doi":"10.1155/2014/850460","DOIUrl":"10.1155/2014/850460","url":null,"abstract":"<p><p>We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA ratios are significant to mitochondrial function and if a material effect on mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6 (radioresistant), and F1 hybrid mouse strains were exposed to total body irradiation. Hepatic genomic DNA was extracted, and mitochondria were isolated. Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling were measured. Radiation influenced strain-specific survival in vivo. F1 hybrid survival was influenced by maternal input. Changes in mitochondrial content corresponded to survival in vivo among the 4 strains. Calcium-induced mitochondrial swelling was strain dependent. Isolated mitochondria from BALB/c mice were significantly more sensitive to calcium overload than mitochondria from C57BL/6 mice. Maternal input partially influenced the recovery effect of radiation on calcium-induced mitochondrial swelling in F1 hybrids; the hybrid with a radiosensitive maternal lineage exhibited a lower rate of recovery. Hybrids had a survival rate that was biased toward maternal input. mtDNA content and mitochondrial permeability transition pores (MPTP) measured in these strains before irradiation reflected a dominant input from the parent. After irradiation, the MPTP opened sooner in radiosensitive and hybrid strains, likely triggering intrinsic apoptotic pathways. These findings have important implications for translation into predictors of radiation sensitivity/resistance. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"850460"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32223795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension.","authors":"Mikael Molin, Ayse Banu Demir","doi":"10.1155/2014/913071","DOIUrl":"10.1155/2014/913071","url":null,"abstract":"<p><p>Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"913071"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32184246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Intimate Relationship between ROS and Insulin Signalling: Implications for Antioxidant Treatment of Fatty Liver Disease.","authors":"Aurèle Besse-Patin,&nbsp;Jennifer L Estall","doi":"10.1155/2014/519153","DOIUrl":"https://doi.org/10.1155/2014/519153","url":null,"abstract":"<p><p>Oxidative stress damages multiple cellular components including DNA, lipids, and proteins and has been linked to pathological alterations in nonalcoholic fatty liver disease (NAFLD). Reactive oxygen species (ROS) emission, resulting from nutrient overload and mitochondrial dysfunction, is thought to be a principal mediator in NAFLD progression, particularly toward the development of hepatic insulin resistance. In the context of insulin signalling, ROS has a dual role, as both a facilitator and inhibitor of the insulin signalling cascade. ROS mediate these effects through redox modifications of cysteine residues affecting phosphatase enzyme activity, stress-sensitive kinases, and metabolic sensors. This review highlights the intricate relationship between redox-sensitive proteins and insulin signalling in the context of fatty liver disease, and to a larger extent, the importance of reactive oxygen species as primary signalling molecules in metabolically active cells. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"519153"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/519153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32212717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the Distribution of the α 3 Na(+)/K(+) ATPase Subunit in Heterozygous Lurcher Purkinje Cells as a Genetic Model of Chronic Depolarization during Development.","authors":"Rebecca McFarland,&nbsp;Hadi S Zanjani,&nbsp;Jean Mariani,&nbsp;Michael W Vogel","doi":"10.1155/2014/152645","DOIUrl":"https://doi.org/10.1155/2014/152645","url":null,"abstract":"<p><p>A common assumption of excitotoxic mechanisms in the nervous system is that the ionic imbalance resulting from overstimulation of glutamate receptors and increased Na(+) and Ca(++) influx overwhelms cellular energy metabolic systems leading to cell death. The goal of this study was to examine how a chronic Na(+) channel leak current in developing Purkinje cells in the heterozygous Lurcher mutant (+/Lc) affects the expression and distribution of the α 3 subunit of the Na(+)/K(+) ATPase pump, a key component of the homeostasis system that maintains ionic equilibrium in neurons. The expression pattern of the catalytic α 3 Na(+)/K(+) ATPase subunit was analyzed by immunohistochemistry, histochemistry, and Western Blots in wild type (WT) and +/Lc cerebella at postnatal days P10, P15, and P25 to determine if there are changes in the distribution of active Na(+)/K(+) ATPase subunits in degenerating Purkinje cells. The results suggest that the expression of the catalytic α 3 subunit is altered in chronically depolarized +/Lc Purkinje cells, although the density of active Na(+)/K(+) ATPase pumps is not significantly altered compared with WT in the cerebellar cortex at P15, and then declines from P15 to P25 in the +/Lc cerebellum as the +/Lc Purkinje cells degenerate. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"152645"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/152645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32251488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necroptosis: molecular signalling and translational implications.","authors":"Claudia Giampietri,&nbsp;Donatella Starace,&nbsp;Simonetta Petrungaro,&nbsp;Antonio Filippini,&nbsp;Elio Ziparo","doi":"10.1155/2014/490275","DOIUrl":"https://doi.org/10.1155/2014/490275","url":null,"abstract":"<p><p>Necroptosis is a form of programmed necrosis whose molecular players are partially shared with apoptotic cell death. Here we summarize what is known about molecular signalling of necroptosis, particularly focusing on fine tuning of FLIP and IAP proteins in the apoptosis/necroptosis balance. We also emphasize necroptosis involvement in physiological and pathological conditions, particularly in the regulation of immune homeostasis. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"490275"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/490275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32168820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}