排序方式: 共有103条查询结果,搜索用时 15 毫秒
21.
Siri Malmgren David G. Nicholls Jalal Taneera Karl Bacos Thomas Koeck Ashkan Tamaddon Rolf Wibom Leif Groop Charlotte Ling Hindrik Mulder Vladimir V. Sharoyko 《The Journal of biological chemistry》2009,284(47):32395-32404
The biochemical mechanisms underlying glucose-stimulated insulin secretion from pancreatic β-cells are not completely understood. To identify metabolic disturbances in β-cells that impair glucose-stimulated insulin secretion, we compared two INS-1-derived clonal β-cell lines, which are glucose-responsive (832/13 cells) or glucose-unresponsive (832/2 cells). To this end, we analyzed a number of parameters in glycolytic and mitochondrial metabolism, including mRNA expression of genes involved in cellular energy metabolism. We found that despite a marked impairment of glucose-stimulated insulin secretion, 832/2 cells exhibited a higher rate of glycolysis. Still, no glucose-induced increases in respiratory rate, ATP production, or respiratory chain complex I, III, and IV activities were seen in the 832/2 cells. Instead, 832/2 cells, which expressed lactate dehydrogenase A, released lactate regardless of ambient glucose concentrations. In contrast, the glucose-responsive 832/13 line lacked lactate dehydrogenase and did not produce lactate. Accordingly, in 832/2 cells mRNA expression of genes for glycolytic enzymes were up-regulated, whereas mitochondria-related genes were down-regulated. This could account for a Warburg-like effect in the 832/2 cell clone, lacking in 832/13 cells as well as primary β-cells. In human islets, mRNA expression of genes such as lactate dehydrogenase A and hexokinase I correlated positively with HbA1c levels, reflecting perturbed long term glucose homeostasis, whereas that of Slc2a2 (glucose transporter 2) correlated negatively with HbA1c and thus better metabolic control. We conclude that tight metabolic regulation enhancing mitochondrial metabolism and restricting glycolysis in 832/13 cells is required for clonal β-cells to secrete insulin robustly in response to glucose. Moreover, a similar expression pattern of genes controlling glycolytic and mitochondrial metabolism in clonal β-cells and human islets was observed, suggesting that a similar prioritization of mitochondrial metabolism is required in healthy human β-cells. The 832 β-cell lines may be helpful tools to resolve metabolic perturbations occurring in Type 2 diabetes. 相似文献
22.
Mohsen Moghoofei Shayan Mostafaei Abolfazl Nesaei Ashkan Etemadi Javid Sadri Nahand Hamed Mirzaei Bahman Rashidi Farhad Babaei Niloofar Khodabandehlou 《Journal of cellular physiology》2019,234(4):3790-3799
Background : Thyroid cancer is a common endocrine malignancy whose incidence has increased in recent years. Several internal and external risk factors are involved in the development of this cancer, such as infectious agents. Evidence supporting the role of viral infection as an etiology for the invasiveness of thyroid cancer is increasing. The aim of this study was to determine the presence of the Epstein–Barr virus (EBV) and the association between viral gene products and thyroid tumor development. Methods : Fifty-seven thyroid cancer specimens were collected from the same number of patients as well as 18 samples from healthy controls. The presence of the EBV genome and the genotyping was examined by polymerase chain reaction (PCR). Also, an enzyme-linked immunosorbent assay and real-time PCR were used to measure the expression levels of viral and cellular genes. Results : The EBV DNA was detected in 71.9% of the samples, and it was also found that the presence of the EBV was associated with increasing development of thyroid tumor. Conclusion : Our results demonstrated that EBV infection may play a role in the development of thyroid tumor. 相似文献
23.
Paramithiotis E Pinard M Lawton T LaBoissiere S Leathers VL Zou WQ Estey LA Lamontagne J Lehto MT Kondejewski LH Francoeur GP Papadopoulos M Haghighat A Spatz SJ Head M Will R Ironside J O'Rourke K Tonelli Q Ledebur HC Chakrabartty A Cashman NR 《Nature medicine》2003,9(7):893-899
Conformational conversion of proteins in disease is likely to be accompanied by molecular surface exposure of previously sequestered amino-acid side chains. We found that induction of beta-sheet structures in recombinant prion proteins is associated with increased solvent accessibility of tyrosine. Antibodies directed against the prion protein repeat motif, tyrosine-tyrosine-arginine, recognize the pathological isoform of the prion protein but not the normal cellular isoform, as assessed by immunoprecipitation, plate capture immunoassay and flow cytometry. Antibody binding to the pathological epitope is saturable and specific, and can be created in vitro by partial denaturation of normal brain prion protein. Conformation-selective exposure of Tyr-Tyr-Arg provides a probe for the distribution and structure of pathologically misfolded prion protein, and may lead to new diagnostics and therapeutics for prion diseases. 相似文献
24.
Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo 总被引:6,自引:0,他引:6
We have used in vivo time-lapse two-photon imaging of single motor neuron axons labeled with GFP combined with labeling of presynaptic vesicle clusters and postsynaptic acetylcholine receptors in Xenopus laevis tadpoles to determine the dynamic rearrangement of individual axon branches and synaptogenesis during motor axon arbor development. Control GFP-labeled axons are highly dynamic during the period when axon arbors are elaborating. Axon branches emerge from sites of synaptic vesicle clusters. These data indicate that motor neuron axon elaboration and synaptogenesis are concurrent and iterative. We tested the role of Candidate Plasticity Gene 15 (CPG15, also known as Neuritin), an activity-regulated gene that is expressed in the developing motor neurons in this process. CPG15 expression enhances the development of motor neuron axon arbors by promoting neuromuscular synaptogenesis and by increasing the addition of new axon branches. 相似文献
25.
Abdominal aortic coarctation above the renal arteries leads to severe hypertension above the stenotic site and provides a model for simultaneous testing of the effects of increased and decreased pressure and consequently shear stress in the same animal. The effects of increased pressure, per se, on oxidative stress and antioxidant enzyme expression is unknown. We studied the protein expressions of antioxidant enzymes and NADPH oxidase (gp91phox subunit) in the aortic segments above and below the stenosis site in sham-operated control and aortic-banded rats at four weeks postoperatively. Compared with the control group, the banded group showed significant up-regulation of NADPH oxidase, catalase (CAT), Cu/Zn superoxide dismutase (SOD) and Mn SOD protein content in the thoracic aorta. In contrast, Mn SOD, Cu/Zn SOD and NADPH oxidase protein abundance were unchanged in the abdominal aortic segment below the stricture where blood pressure is not elevated, whereas CAT protein abundance was also elevated in the abdominal aorta. No changes were noted for glutathione peroxidase (GPX) protein content either in the thoracic or abdominal aortic segments. Coarctation-induced hypertension is associated with increased aortic CAT, Cu/Zn SOD, Mn SOD and NADPH oxidase protein expression. The up-regulation of NADPH oxidase increases reactive oxygen species (ROS) generation noted in the present study and contributes to inactivation of nitric oxide (NO) as shown previously in this model. Upregulation of antioxidant enzymes may be a compensatory response in the face of elevated pressure and oxidative stress. The normality of protein abundance in the abdominal aorta wherein blood pressure is not elevated points to the role of baromechanical factors, as opposed to circulating humoral factors that were similar in both segments, as a mechanism responsible for increased antioxidant enzyme expression. 相似文献
26.
Babu M Díaz-Mejía JJ Vlasblom J Gagarinova A Phanse S Graham C Yousif F Ding H Xiong X Nazarians-Armavil A Alamgir M Ali M Pogoutse O Pe'er A Arnold R Michaut M Parkinson J Golshani A Whitfield C Wodak SJ Moreno-Hagelsieb G Greenblatt JF Emili A 《PLoS genetics》2011,7(11):e1002377
As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. 相似文献
27.
John A. Rennick Ara Nazarian Vahid Entezari James Kimbaris Alan Tseng Aidin Masoudi Hamid Nayeb-Hashemi Ashkan Vaziri Brian D. Snyder 《Journal of biomechanics》2013
Finite element analysis (FEA), CT based structural rigidity analysis (CTRA) and mechanical testing is performed to assess the compressive failure load of rat tibia with simulated lytic defects. 相似文献
28.
Kamran Mohamad Reza Zargan Jamil alikhani Hani Keshavarz Hajinoormohamadi Ashkan 《International journal of peptide research and therapeutics》2020,26(4):1819-1828
International Journal of Peptide Research and Therapeutics - Bee venom (BV) has variety of properties, such as anti-inflammatory potential and anti-cancer activity.It has been shown that BV has... 相似文献
29.
Divanbeigi Ashkan Nasehi Mohammad Vaseghi Salar Amiri Sepideh Zarrindast Mohammad-Reza 《Neurochemical research》2020,45(11):2631-2640
Neurochemical Research - Tropisetron and Granisetorn are 5-HT3 antagonists with antiemetic effects. Tropisetron also has a partial agonistic effect on alpha-7 nicotinic acetylcholine receptors... 相似文献
30.
Andrew Schoenrock Bahram Samanfar Sylvain Pitre Mohsen Hooshyar Ke Jin Charles A Phillips Hui Wang Sadhna Phanse Katayoun Omidi Yuan Gui Md Alamgir Alex Wong Fredrik Barren?s Mohan Babu Mikael Benson Michael A Langston James R Green Frank Dehne Ashkan Golshani 《BMC bioinformatics》2014,15(1)