International Journal of Cell Biology最新文献

{"title":"The role of hyaluronan in innate defense responses of the intestine.","authors":"Carol A de la Motte,&nbsp;Sean P Kessler","doi":"10.1155/2015/481301","DOIUrl":"https://doi.org/10.1155/2015/481301","url":null,"abstract":"<p><p>Hyaluronan is an abundant extracellular matrix component prevalent in the vertebrate intestinal tract. Here we discuss what is known about hyaluronan distribution during homeostasis and inflammatory diseases of the gut and discuss ways in which this glycosaminoglycan can participate in regulating innate host defense mechanisms. These natural responses include mechanisms promoting rapid leukocyte recruitment after bacterial challenge/colon tissue damage as well as promoting epithelial defense mechanisms in the intestine. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"481301"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/481301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33260517","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":"Hyaluronan Synthase: The Mechanism of Initiation at the Reducing End and a Pendulum Model for Polysaccharide Translocation to the Cell Exterior.","authors":"Paul H Weigel","doi":"10.1155/2015/367579","DOIUrl":"https://doi.org/10.1155/2015/367579","url":null,"abstract":"<p><p>Hyaluronan (HA) biosynthesis has been studied for over six decades, but our understanding of the biochemical details of how HA synthase (HAS) assembles HA is still incomplete. Class I family members include mammalian and streptococcal HASs, the focus of this review, which add new intracellular sugar-UDPs at the reducing end of growing hyaluronyl-UDP chains. HA-producing cells typically create extracellular HA coats (capsules) and also secrete HA into the surrounding space. Since HAS contains multiple transmembrane domains and is lipid-dependent, we proposed in 1999 that it creates an intraprotein HAS-lipid pore through which a growing HA-UDP chain is translocated continuously across the cell membrane to the exterior. We review here the evidence for a synthase pore-mediated polysaccharide translocation process and describe a possible mechanism (the Pendulum Model) and potential energy sources to drive this ATP-independent process. HA synthases also synthesize chitin oligosaccharides, which are created by cleavage of novel oligo-chitosyl-UDP products. The synthesis of chitin-UDP oligomers by HAS confirms the reducing end mechanism for sugar addition during HA assembly by streptococcal and mammalian Class I enzymes. These new findings indicate the possibility that HA biosynthesis is initiated by the ability of HAS to use chitin-UDP oligomers as self-primers. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"367579"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/367579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34092965","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":"Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery.","authors":"Suniti Misra,&nbsp;Vincent C Hascall,&nbsp;Ilia Atanelishvili,&nbsp;Ricardo Moreno Rodriguez,&nbsp;Roger R Markwald,&nbsp;Shibnath Ghatak","doi":"10.1155/2015/537560","DOIUrl":"https://doi.org/10.1155/2015/537560","url":null,"abstract":"<p><p>The outcome of patients with cancer has improved significantly in the past decade with the incorporation of drugs targeting cell surface adhesive receptors, receptor tyrosine kinases, and modulation of several molecules of extracellular matrices (ECMs), the complex composite of collagens, glycoproteins, proteoglycans, and glycosaminoglycans that dictates tissue architecture. Cancer tissue invasive processes progress by various oncogenic strategies, including interfering with ECM molecules and their interactions with invasive cells. In this review, we describe how the ECM components, proteoglycans and glycosaminoglycans, influence tumor cell signaling. In particular this review describes how the glycosaminoglycan hyaluronan (HA) and its major receptor CD44 impact invasive behavior of tumor cells, and provides useful insight when designing new therapeutic strategies in the treatment of cancer. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"537560"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/537560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34240815","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":"Modulation Effects of Curcumin on Erythrocyte Ion-Transporter Activity.","authors":"Prabhakar Singh,&nbsp;Syed Ibrahim Rizvi","doi":"10.1155/2015/630246","DOIUrl":"https://doi.org/10.1155/2015/630246","url":null,"abstract":"<p><p>Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the yellow biphenolic pigment isolated from turmeric (Curcuma longa), has various medicinal benefits through antioxidation, anti-inflammation, cardiovascular protection, immunomodulation, enhancing of the apoptotic process, and antiangiogenic property. We explored the effects of curcumin in vitro (10(-5) M to 10(-8) M) and in vivo (340 and 170 mg/kg b.w., oral) on Na(+)/K(+) ATPase (NKA), Na(+)/H(+) exchanger (NHE) activity, and membrane lipid hydroperoxides (ROOH) in control and experimental oxidative stress erythrocytes of Wistar rats. As a result, we found that curcumin potently modulated the membrane transporters activity with protecting membrane lipids against hydro-peroxidation in control as well as oxidatively challenged erythrocytes evidenced by stimulation of NKA, downregulation of NHE, and reduction of ROOH in the membrane. The observed results corroborate membrane transporters activity with susceptibility of erythrocyte membrane towards oxidative damage. Results explain the protective mechanism of curcumin against oxidative stress mediated impairment in ions-transporters activity and health beneficial effects. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"630246"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/630246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34218651","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":"Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways.","authors":"Shannon M Ruppert,&nbsp;Ben A Falk,&nbsp;S Alice Long,&nbsp;Paul L Bollyky","doi":"10.1155/2015/614297","DOIUrl":"https://doi.org/10.1155/2015/614297","url":null,"abstract":"<p><p>Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"614297"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/614297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34240816","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":"Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases.","authors":"Larry S Sherman,&nbsp;Steven Matsumoto,&nbsp;Weiping Su,&nbsp;Taasin Srivastava,&nbsp;Stephen A Back","doi":"10.1155/2015/368584","DOIUrl":"https://doi.org/10.1155/2015/368584","url":null,"abstract":"<p><p>The glycosaminoglycan hyaluronan (HA), a component of the extracellular matrix, has been implicated in regulating neural differentiation, survival, proliferation, migration, and cell signaling in the mammalian central nervous system (CNS). HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity. HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes. Insults to the CNS lead to long-term elevation of HA within damaged tissues, which is linked at least in part to increased transcription of HA synthases. HA accumulation is often accompanied by elevated expression of at least some transmembrane HA receptors including CD44. Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities. A number of studies, for example, suggest that both the removal of high molecular weight HA and the accumulation of hyaluronidase-generated HA digestion products can impact CNS injuries through mechanisms that include the regulation of progenitor cell differentiation and proliferation. These studies, reviewed here, suggest that targeting HA synthesis, catabolism, and signaling are all potential strategies to promote CNS repair. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"368584"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/368584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34240813","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":"Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective.","authors":"Sajina Shakya,&nbsp;Yan Wang,&nbsp;Judith A Mack,&nbsp;Edward V Maytin","doi":"10.1155/2015/701738","DOIUrl":"https://doi.org/10.1155/2015/701738","url":null,"abstract":"<p><p>Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia. In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels. Potential mechanisms through which exposure to high glucose levels causes a loss of the glycocalyx on the endothelium and accelerates the recruitment of leukocytes, creating a proinflammatory environment, are discussed in detail. Hyperglycemia also affects other cells in the immediate perivascular area, including pericytes and smooth muscle cells, through exposure to increased cytokine levels and through glucose elevations in the interstitial fluid. Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"701738"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/701738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34240817","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":"Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer.","authors":"Marisa Shiina,&nbsp;Lilly Y W Bourguignon","doi":"10.1155/2015/989070","DOIUrl":"https://doi.org/10.1155/2015/989070","url":null,"abstract":"<p><p>We determined that human head and neck cancer cells (HSC-3 cell line) contain a subpopulation displaying cancer stem cell (CSC) properties and are very tumorigenic. Specifically, we investigated whether different sizes of hyaluronan (HA) (e.g., 5 kDa, 20 kDa, 200 kDa, or 700 kDa-HA-sizes) play a role in regulating these CSCs. First, we observed that 200 kDa-HA (but not other sizes of HA) preferentially induces certain stem cell marker expression resulting in self-renewal and clonal formation of these cells. Further analyses indicate that 200 kDa-HA selectively stimulates the expression of a panel of microRNAs (most noticeably miR-10b) in these CSCs. Survival protein (cIAP-1) expression was also stimulated by 200 kDa-HA in these CSCs leading to cisplatin resistance. Furthermore, our results indicate that the anti-miR-10 inhibitor not only decreases survival protein expression, but also increases chemosensitivity of the 200 kDa-HA-treated CSCs. These findings strongly support the contention that 200 kDa-HA plays a pivotal role in miR-10 production leading to survival protein upregulation and chemoresistance in CSCs. Together, our findings suggest that selective activation of oncogenic signaling by certain sizes of HA (e.g., 200 kDa-HA) may be instrumental in the formation of CSC functions leading to tumor cell survival and chemoresistance in head and neck cancer progression. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"989070"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/989070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34138716","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":"Intermittent Compressive Stress Enhanced Insulin-Like Growth Factor-1 Expression in Human Periodontal Ligament Cells.","authors":"Jittima Pumklin,&nbsp;Jeeranan Manokawinchoke,&nbsp;Kanokporn Bhalang,&nbsp;Prasit Pavasant","doi":"10.1155/2015/369874","DOIUrl":"https://doi.org/10.1155/2015/369874","url":null,"abstract":"<p><p>Mechanical force was shown to promote IGF-1 expression in periodontal ligament both in vitro and in vivo. Though the mechanism of this effect has not yet been proved, here we investigated the molecular mechanism of intermittent mechanical stress on IGF-1 expression. In addition, the role of hypoxia on the intermittent compressive stress on IGF-1 expression was also examined. In this study, human periodontal ligament cells (HPDLs) were stimulated with intermittent mechanical stress for 24 hours. IGF-1 expression was examined by real-time polymerase chain reaction. Chemical inhibitors were used to determine molecular mechanisms of these effects. For hypoxic mimic condition, the CoCl2 supplementation was employed. The results showed that intermittent mechanical stress dramatically increased IGF-1 expression at 24 h. The pretreatment with TGF-β receptor I or TGF-β1 antibody could inhibit the intermittent mechanical stress-induced IGF-1 expression. Moreover, the upregulation of TGF-β1 proteins was detected in intermittent mechanical stress treated group. Correspondingly, the IGF-1 expression was upregulated upon being treated with recombinant human TGF-β1. Further, the hypoxic mimic condition attenuated the intermittent mechanical stress and rhTGF-β1-induced IGF-1 expression. In summary, this study suggests intermittent mechanical stress-induced IGF-1 expression in HPDLs through TGF-β1 and this phenomenon could be inhibited in hypoxic mimic condition. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"369874"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/369874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33413967","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":"Cell biology of cysteine-based molecular switches.","authors":"Christian Appenzeller-Herzog,&nbsp;Kenji Inaba,&nbsp;Agnès Delaunay-Moisan","doi":"10.1155/2014/157038","DOIUrl":"https://doi.org/10.1155/2014/157038","url":null,"abstract":"Reversible posttranslational protein modifications form the mechanistic basis for the reception and propagation of biological signals in cells. Besides other modifications such as phosphorylation, acetylation, ADP-ribosylation, and ubiquitylation, reduction-oxidation (redox) processes allow reversible structure-function modulation of proteins, which serve as molecular on-off switches in cell biology. Although many protein-bound amino acids and even the peptide backbone can react with oxidizing metabolites during oxidative stress, only three amino acids adopt reversible redox modifications: cysteine, selenocysteine, and methionine. Among these, cysteine-based molecular switches are by far the most prevalent and best studied. Cysteine switches (or “sulfur switches”) respond in heterogeneous, context-dependent manner to a variety of stimuli (endogenous metabolites, chemicals from the diet, xenobiotics, or air oxidants) by direct modification. Common covalent modifications of cysteines include intra- or intermolecular protein-protein disulfide-bond formation, S-glutathionylation, S-cysteinylation, S-nitrosylation, sulfoxidation, and sulfhydration. \u0000 \u0000Catalyzed, redox-dependent on-off cycles of cysteine centers in proteins regulate processes as diverse as protein folding, aggregation, and trafficking, enzymatic activity, metal chelation, DNA, RNA, protein, or membrane binding, and channel opening. In this special issue, we have attempted to illustrate the versatility of cysteine-based protein regulation and its impact on the physiology of cells and organisms. \u0000 \u0000In both the secretory pathway and the mitochondrial intermembrane space (IMS), protein maturation often requires the introduction of disulfide crosslinks to promote or maintain protein structure. During this process known as oxidative protein folding, introduced disulfide bridges can be reshuffled, until the native conformation is achieved. Dedicated oxidative folding catalysts, as reviewed by Y. Onda, exist in the endoplasmic reticulum (ER), IMS, and chloroplasts in plant cells as well as in the extracellular space. The disulfide-generating machineries in ER and IMS are conserved in plants, fungi, and animals. Evolutionary and mechanistic aspects of disulfide-bond formation in IMS are discussed by M. Fischer and J. Riemer. Interestingly, the core components of this machinery, Erv1/ALR and Mia40, have additional, poorly understood functions in liver regeneration and hypoxia response, which are likely fulfilled through mechanisms other than oxidative folding in IMS. \u0000 \u0000Two contributions are concerned with the involvement of cysteines in the regulation of antibody secretion and differentiation of B lymphocytes. The review article by T. Anelli and E. van Anken enlightens how cysteine redox status acts as a quality control checkpoint to ensure that only mature IgM antibodies leave the compartments of the early secretory pathway en route to the blood stream. Immature antibodies are tagged with a fr","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"157038"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/157038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32191232","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}