Trends in cell & molecular biology最新文献

{"title":"Upregulation of non-canonical Wnt ligands and oxidative glucose metabolism in NASH induced by methionine-choline deficient diet.","authors":"Lixin Zhu, S. Baker, Abdul R. Shahein, S. Choudhury, Wensheng Liu, Tavleen Bhatia, R. Baker, Techung Lee","doi":"10.31300/TCMB.13.2018.47-56","DOIUrl":"https://doi.org/10.31300/TCMB.13.2018.47-56","url":null,"abstract":"Wnt ligands regulate metabolic pathways, and dysregulation of Wnt signaling contributes to chronic inflammatory disease. A knowledge gap exists concerning the role of aberrant Wnt signaling in non-alcoholic steatohepatitis (NASH), which exhibits metabolic syndrome and inflammation. Using a mouse model of methionine-choline deficient diet (MCDD)-induced NASH, we investigated the Wnt signaling pathways in relation to hepatic glucose oxidation. Mice fed the MCD diet for 6 weeks developed prominent NASH marked by macrovesicular steatosis, inflammation and lipid peroxidation. qPCR analysis reveals differential hepatic expression of canonical and non-canonical Wnt ligands. While expression of Wnt3a was decreased in NASH vs chow diet control, expression of Wnt5a and Wnt11 were increased 3 fold and 15 fold, respectively. Consistent with activation of non-canonical Wnt signaling, expression of the alternative Wnt receptor ROR2 was increased 5 fold with no change in LRP6 expression. Activities of the metabolic enzymes glucokinase, phosphoglucoisomerase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and pyruvate dehydrogenase were all elevated by MCDD. NASH-driven glucose oxidation was accompanied by a 6-fold increase in lactate dehydrogenase (LDH)-B with no change in LDH-A. In addition, glucose-6-phosphate dehydrogenase, the regulatory and NADPH-producing enzyme of the pentose phosphate pathway, was elevated in NASH. These data support a role of accelerated glucose oxidation in the development of NASH, which may be driven by non-canonical Wnt signaling.","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"7 1","pages":"47-56"},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85179006","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}

{"title":"CYP1B1: A key regulator of redox homeostasis.","authors":"Juliana Falero-Perez, Yong-Seok Song, Christine M Sorenson, Nader Sheibani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>CYP1B1 is a member of the CYP1 subfamily of CYP superfamily of enzymes, which contains three members, CYP1A1, CYP1A2, and CYP1B1. CYP1B1 is expressed in both adult and fetal human extrahepatic tissues, including the parenchymal and stromal cells of most organs. Mutations in the CYP1B1 gene are linked to the development of primary congenital glaucoma in humans. However, the underlying mechanisms remain unknown. Using <i>Cyp1b1</i>-deficient mice, we showed that CYP1B1 is constitutively expressed in retinal vascular cells with a significant role in retinal neovascularization during oxygen-induced ischemic retinopathy. We also showed CYP1B1 is constitutively expressed in trabecular meshwork (TM) cells and its expression plays a significant role in the normal development and function of the TM tissue. We have observed that germline deletion of <i>Cyp1b1</i> is associated with increased oxidative stress in the retinal vascular and TM cells in culture, and retinal and TM tissue in vivo. We showed increased oxidative stress was responsible for altered production of the extracellular matrix proteins and had a significant impact on cellular integrity and function of these tissues. Collectively, our studies have established an important role for CYP1B1 expression in modulation of tissue integrity and function through the regulation of cellular redox homeostasis and extracellular microenvironment.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"13 ","pages":"27-45"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422340/pdf/nihms-1016915.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37237922","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":"Spontaneous and cytokine-induced hole formation in epithelial cell layers: Implications for barrier function studies with the gingival cell culture, Gie-3B11, and other epithelial models.","authors":"Elizabeth Rybakovsky,&nbsp;Nicole B Buleza,&nbsp;Kevt'her Hoxha,&nbsp;Katherine M DiGuilio,&nbsp;Elizabeth S McCluskey,&nbsp;Cary L Friday,&nbsp;Patrick J Callaghan,&nbsp;Daniil V Moskalenko,&nbsp;Biao Zuo,&nbsp;Sunil Thomas,&nbsp;James M Mullin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epithelial barrier function studies often attribute alterations in barrier function to induced changes in tight junctional (TJ) complexes. The occurrence of spontaneous and cytokine-induced, focal cell detachment in cell layers of the human gingival epithelial cell line, Gie-3B11, highlights the danger of this assumption without confirmatory experimentation. Gie-3B11 cell layers manifest morphological polarity, TJ complexes and barrier function after confluence but fail to then maintain a stable epithelial barrier. Transepithelial electrical resistance rises to over 100 ohms x cm² a few days after seeding cell layers at a confluent density, but then spontaneously declines, with simultaneous, inverse changes in transepithelial ¹⁴C-D-mannitol diffusion rates. This barrier decline correlates with the appearance of focal cell detachment/hole formation in cell layers. Both barrier compromise (decreased electrical resistance; increased ¹⁴C-D-mannitol leak) and hole formation are accelerated and exaggerated by exposing cell layers to proinflammatory cytokines. Both are inhibited by increasing the basal-lateral medium compartment volume, suggesting that cell layers are secreting factor(s) across their basal-lateral surfaces that are causal to hole formation. The molecular mechanism of cell death/detachment here is not as significant as the implications of hole formation for the correct interpretation of barrier function studies. Barrier changes in any epithelial model should be attributed to induced changes in TJ complexes only after thorough investigation.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"13 ","pages":"99-114"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542284/pdf/nihms-1030024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37301292","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":"Upregulation of non-canonical Wnt ligands and oxidative glucose metabolism in NASH induced by methionine-choline deficient diet.","authors":"Lixin Zhu,&nbsp;Susan S Baker,&nbsp;Abdul Shahein,&nbsp;Shelly Choudhury,&nbsp;Wensheng Liu,&nbsp;Tavleen Bhatia,&nbsp;Robert D Baker,&nbsp;Techung Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Wnt ligands regulate metabolic pathways, and dysregulation of Wnt signaling contributes to chronic inflammatory disease. A knowledge gap exists concerning the role of aberrant Wnt signaling in non-alcoholic steatohepatitis (NASH), which exhibits metabolic syndrome and inflammation. Using a mouse model of methionine-choline deficient diet (MCDD)-induced NASH, we investigated the Wnt signaling pathways in relation to hepatic glucose oxidation. Mice fed the MCD diet for 6 weeks developed prominent NASH marked by macrovesicular steatosis, inflammation and lipid peroxidation. qPCR analysis reveals differential hepatic expression of canonical and non-canonical Wnt ligands. While expression of Wnt3a was decreased in NASH vs chow diet control, expression of Wnt5a and Wnt11 were increased 3 fold and 15 fold, respectively. Consistent with activation of non-canonical Wnt signaling, expression of the alternative Wnt receptor ROR2 was increased 5 fold with no change in LRP6 expression. Activities of the metabolic enzymes glucokinase, phosphoglucoisomerase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and pyruvate dehydrogenase were all elevated by MCDD. NASH-driven glucose oxidation was accompanied by a 6-fold increase in lactate dehydrogenase (LDH)-B with no change in LDH-A. In addition, glucose-6-phosphate dehydrogenase, the regulatory and NADPH-producing enzyme of the pentose phosphate pathway, was elevated in NASH. These data support a role of accelerated glucose oxidation in the development of NASH, which may be driven by non-canonical Wnt signaling.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"13 ","pages":"47-56"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407712/pdf/nihms-1015795.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37042299","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":"Chronic pain following spinal cord injury: Current approaches to cellular and molecular mechanisms.","authors":"Jessica R Yasko, Richard E Mains","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Traumatic spinal cord injury (SCI) has devastating implications for patients, including a high prevalence of chronic pain. Despite advancements in our understanding of the mechanisms involved post-SCI, there are no effective treatments for chronic pain following injury. The development of new treatment interventions for pain is needed, but this requires improved models to assess injury-related cellular, neurophysiological and molecular changes in the spinal cord. Here, we will discuss recent animal models for SCI, molecular screening for altered patterns of gene expression, and the importance of injury severity and timing after SCI.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"13 ","pages":"67-84"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869846/pdf/nihms-1656493.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25351293","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":"A role for ataxia telangiectasia mutated in insulin-independent stimulation of glucose transport.","authors":"Larry D Spears, Allyson L Renth, Michael R McKuin, Anne R Kennedy, Stanley Andrisse, Nell E Briggs, Jonathan S Fisher","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Literature reports suggest that ataxia telangiectasia mutated (ATM) can activate the AMP-activated protein kinase (AMPK), a protein that can stimulate glucose transport in skeletal muscle. We hypothesized that 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, would increase glucose transport in mouse extensor digitorum longus (EDL) muscles in an ATM-dependent manner. AICAR-stimulated glucose transport was prevented by the ATM inhibitor KU-55933 despite normal stimulation of AMPK phosphorylation. Consistent with this, AICAR caused AMPK phosphorylation but not an increase of glucose transport in ATM-deficient (ATM-/-) muscles. S231 of TBC1D1 matches the sequence motif of ATM substrates, and phosphorylation of this site is known to inhibit TBC1D1 and lead to increased glucose transport. Accordingly, we assessed TBC1D1 phosphorylation and found that AICAR-stimulated phosphorylation of TBC1D1 at S231 did not occur in ATM-/- muscles. However, activation of ATM without activation of AMPK was insufficient to increase TBC1D1 phosphorylation. The data suggest that ATM plays a role in AICAR-stimulated glucose transport downstream of AMPK.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"12 ","pages":"49-56"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287632/pdf/nihms951331.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36820432","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":"Aging and the Krüppel-like factors.","authors":"Paishiun N Hsieh, David R Sweet, Liyan Fan, Mukesh K Jain","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mammalian Krüppel-like factors (KLFs) are a family of zinc-finger containing transcription factors with diverse patterns of expression and a wide array of cellular functions. While their roles in mammalian physiology are well known, there is a growing appreciation for their roles in modulating the fundamental progression of aging. Here we review the current knowledge of Krüppel-like factors with a focus on their roles in processes regulating aging and age-associated diseases.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"12 ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798252/pdf/nihms937159.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35807274","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":"Hepatotoxicity and Ultra Structural Changes in Wistar Rats treated with Al₂O₃ Nanomaterials.","authors":"S Anitha Kumari, P Madhusudhanachary, Anita K Patlolla, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study was designed to evaluate the hepatotoxicity of aluminium oxide (Al₂O₃). To achieve this objective, Al₂O₃ of three different sizes (30nm, 40nm and bulk) was orally administered for 28 days to 9 groups of 10 Wistar rats each, at the dose of 500, 1000 and 2000 mg/Kg/rat. A tenth group of 10 rats received distilled water and served as control. After 28 days of exposure, the animals were sacrificed and the serum was collected and tested for the activity levels of aminotransferases (AST or GOT and ALT or GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) enzymes following standard testing methods. Reduced glutathione (GSH) content was also measured in the liver tissue to study the oxidative stress. A histopathological evaluation was also performed to determine the extent of liver injury. Study results indicated that the activity of both the aminotransferases (AST and ALT), ALP and LDH increased significantly in Al₂O₃ treated rats compared to control animals. The increase was found to be more pronounced with Al₂O₃ - 30nm followed by Al₂O₃ - 40nm and Al₂O₃ - bulk treated rats in a dose dependent manner. However reduced glutathione content showed a decline in the activity. Ultra structural assessment showed significant morphological changes in the liver tissue in accordance with biochemical parameters. Taken together, the results of this study demonstrated that Al₂O₃ is hepatotoxic and the smaller size of this nanomaterial appeared to be the most toxic while the compound in the bulk form seemed to be the least toxic.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"11 ","pages":"77-88"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505674/pdf/nihms874439.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35166466","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":"Role of NG2 proteoglycan in macrophage recruitment to brain tumors and sites of CNS demyelination.","authors":"Pilar Cejudo-Martin, Karolina Kucharova, William B Stallcup","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Macrophage infiltration is a factor in most if not all inflammatory pathologies. Understanding molecular interactions that underlie this process is therefore important for our ability to modulate macrophage behavior for therapeutic purposes. Our studies show that cell surface expression of the nerveglial antigen 2 (NG2) proteoglycan is important for the ability of macrophages to colonize both brain tumors and sites of central nervous system (CNS) demyelination. Myeloid-specific ablation of NG2 using LysM-Cre deleter mice results in large decreases in macrophage abundance in both an intracranial melanoma model and a lysolecithin model of spinal cord demyelination. In the melanoma model, decreased macrophage recruitment in the NG2 null mice leads to diminished tumor growth. In line with observations in the literature, this phenomenon is based in part on deficits in tumor vascularization that result from loss of pericyte interaction with endothelial cells in the absence of a macrophage-derived factor(s). In the demyelination model, decreased macrophage infiltration in the NG2 null mice is associated with an initial reduction in lesion size, but nevertheless also with deficits in repair of the lesion. Diminished myelin repair is due not only to reduced clearance of myelin debris, but also to decreased proliferation/recruitment of oligodendrocyte progenitor cells in the absence of a macrophage-derived factor(s). Thus, in both models macrophages have secondary effects on other cell types that are important for progression of the specific pathology. Efforts are underway to identify mechanisms by which NG2 influences macrophage recruitment and by which macrophages signal to other cell types involved in the pathologies.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"11 ","pages":"55-65"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464760/pdf/nihms866696.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35079541","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":"Structural comparison of bacterial multidrug efflux pumps of the major facilitator superfamily.","authors":"Indrika Ranaweera, Ugina Shrestha, K C Ranjana, Prathusha Kakarla, T Mark Willmon, Alberto J Hernandez, Mun Mun Mukherjee, Sharla R Barr, Manuel F Varela","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The biological membrane is an efficient barrier against water-soluble substances. Solute transporters circumvent this membrane barrier by transporting water-soluble solutes across the membrane to the other sides. These transport proteins are thus required for all living organisms. Microorganisms, such as bacteria, effectively exploit solute transporters to acquire useful nutrients for growth or to expel substances that are inhibitory to their growth. Overall, there are distinct types of related solute transporters that are grouped into families or superfamilies. Of these various transporters, the major facilitator superfamily (MFS) represents a very large and constantly growing group and are driven by solute- and ion-gradients, making them passive and secondary active transporters, respectively. Members of the major facilitator superfamily transport an extreme variety of structurally different substrates such as antimicrobial agents, amino acids, sugars, intermediary metabolites, ions, and other small molecules. Importantly, bacteria, especially pathogenic ones, have evolved multidrug efflux pumps which belong to the major facilitator superfamily. Furthermore, members of this important superfamily share similar primary sequences in the form of highly conserved sequence motifs that confer useful functional properties during transport. The transporters of the superfamily also share similarities in secondary structures, such as possessing 12- or 14-membrane spanning α-helices and the more recently described 3-helix structure repeat element, known as the MFS fold. The three-dimensional structures of bacterial multidrug efflux pumps have been determined for only a few members of the superfamily, all drug pumps of which are surprisingly from <i>Escherichia coli</i>. This review briefly summarizes the structural properties of the bacterial multidrug efflux pumps of the major facilitator superfamily in a comparative manner and provides future directions for study.</p>","PeriodicalId":23241,"journal":{"name":"Trends in cell & molecular biology","volume":"10 ","pages":"131-140"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822553/pdf/nihms757244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34390936","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}