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Different modes of sodium-D-glucose cotransporter-mediated D-glucose uptake regulation in Caco-2 cells 总被引:1,自引:0,他引:1
Khoursandi S Scharlau D Herter P Kuhnen C Martin D Kinne RK Kipp H 《American journal of physiology. Cell physiology》2004,287(4):C1041-C1047
We recently reported that a considerable amount of the sodium-D-glucose cotransporter SGLT1 present in Caco-2 cells, a model for human enterocytes, is located in intracellular compartments attached to microtubules (Kipp H, Khoursandi S, Scharlau D, and Kinne RKH. Am J Physiol Cell Physiol 285: C737C749, 2003). A similar distribution pattern was also observed in enterocytes in thin sections from human jejunum, highlighting the validity of the Caco-2 cell model. Fluorescent surface labeling of live Caco-2 cells revealed that the intracellular compartments containing SGLT1 were accessible by endocytosis. To elucidate the role of endosomal SGLT1 in the regulation of sodium-dependent D-glucose uptake into enterocytes, we compared SGLT1-mediated D-glucose uptake into Caco-2 cells with the subcellular distribution of SGLT1 after challenging the cells with different stimuli. Incubation (90 min) of Caco-2 cells with mastoparan (50 µM), a drug that enhances apical endocytosis, shifted a large amount of SGLT1 from the apical membrane to intracellular sites and significantly reduced sodium-dependent -[14C]methyl-D-glucose uptake (60%). We also investigated the effect of altered extracellular D-glucose levels. Cells preincubated (1 h) with D-glucose-free medium exhibited significantly higher sodium-dependent -[14C]methyl-D-glucose uptake (+45%) than did cells preincubated with high D-glucose medium (100 mM, 1 h). Interestingly, regulation of SGLT1-mediated D-glucose uptake into Caco-2 cells by extracellular D-glucose levels occurred without redistribution of cellular SGLT1. These data suggest that, pharmacologically, D-glucose uptake can be regulated by a shift of SGLT1 between the plasma membrane and the endosomal pool; however, regulation by the physiological substrate D-glucose can be explained only by an alternative mechanism. endosomes; enterocytes 相似文献
104.
Mapping global histone acetylation patterns to gene expression 总被引:37,自引:0,他引:37
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Hattab AS 《Developing world bioethics》2004,4(2):160-172
The unprecedented progress in bio-medical sciences and technology during the last few decades has resulted in great transformations in the concepts of health and disease, health systems and healthcare organisation and practices. Those changes have been accompanied by the emergence of a broad range of ethical dilemmas that confront health professionals more frequently. The classical Hippocratic ethical principles, though still retaining their relevance and validity, have become insufficiently adequate in an increasing range of problems and situations. Healthcare that has been practised for centuries on the basis of a direct doctor-patient relationship has been increasingly transformed into a more complex process integrating the health-team, the patient (healthcare seeker) and the community. Systematic review of the specialised literatures revealed that Healthcare Ethics education has become a basic requirement for any training programme for health professionals, and should cover the different stages of undergraduate, postgraduate and continuing education. Both theoretical foundations and practical skills are required for the appropriate ethical reasoning, ethical attitude and decision-making abilities. There is growing evidence that physicians' professional and moral development is not only determined by the formal curriculum of ethics; rather more, it is determined by the moral environment of the professional practice, the 'hidden curriculum' which deserves serious consideration by medical education. 相似文献
107.
(E)- and (Z)-1,2,4-triazolylchromanone oxime ethers as conformationally constrained antifungals 总被引:1,自引:0,他引:1
Emami S Falahati M Banifatemi A Amanlou M Shafiee A 《Bioorganic & medicinal chemistry》2004,12(15):3971-3976
A series of 1,2,4-triazolylchromanone oxime ethers were synthesized and tested for in vitro antifungal activity. Many of these derivatives exhibit high activity against Candida albicans, Saccharomyces cerevisiae, Aspergillus niger and Microsporum gypseum. 相似文献
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Saeed M 《Experimental biology and medicine (Maywood, N.J.)》2001,226(5):367-376
New concepts regarding the assessment of ischemic myocardial injuries have been addressed in this Minireview using magnetic resonance imaging (MRI). MRI, with its different techniques, brings not only anatomic, but also physiologic, information on ischemic heart disease. It has the ability to measure identical parameters in preclinical and clinical studies. MRI techniques provide the ideal package for repeated and noninvasive assessment of myocardial anatomy, viability, perfusion, and function. MR contrast agents can be applied in a variety of ways to improve MRI sensitivity for detecting and assessing ischemically injured myocardium. With MR contrast agents protocol, it becomes possible to identify ischemic, acutely infarcted, and peri-infarcted myocardium in occlusive and reperfused infarctions. Necrosis specific and nonspecific extracellular contrast-enhanced MRI has been used to assess myocardial viability. Contrast-enhanced perfusion MRI can explore the disturbances in large (angiography) and small coronary arteries (myocardial perfusion) as the underlying cause of myocardial dysfunction. Perfusion MRI has been used to measure myocardial perfusion (ml/min/g) and to demonstrate the difference in transmural myocardial blood flow. Information on no-reflow phenomenon is derived from dynamic changes in regional signal intensity after bolus injection of MR contrast agents. Another development is the near future availability of blood pool MR contrast agents. These agents are able to assess microvascular permeability and integrity and are advantageous in MR angiography (MRA) due to their persistence in the blood. Noncontrast-enhanced MRI such as cine MRI at rest/stress, sodium MRI, and MR spectroscopy also have the potential to noninvasively assess myocardial viability in patients. Futuristic applications for MRI in the heart will focus on identifying coronary artery disease at an early stage and the beneficial effects of new therapeutic agents such as intra-arterial gene therapy. MR techniques will have great future in the drug discovery process and in testing the effects of drugs on myocardial biochemistry, physiology, and morphology. Molecular imaging is going to bloom in this decade. 相似文献
109.
The impact of age-related resistance on the regulation of population dynamics of adult Trichuris suis was investigated in an experimental pig model. Helminth-na?ve pigs varying in age from five weeks to four years were infected with T. suis to determine susceptibility to infection. Sows had a significantly lower establishment of adult T. suis worms compared with weaner pigs. Adult worm populations were highly overdispersed in both sows and grower pigs contrasted by a more even distribution among weaner pigs. Sows had significantly lower worm fecundities compared to weaner and grower pigs; T. suis from grower pigs, in turn, had reduced fecundity compared to worms in weaner pigs. In conclusion, we provide the first controlled experimental evidence that age-related resistance to T. suis occurs in pigs. 相似文献
110.
Navarro CE Saeed SA Murdock C Martinez-Fuentes AJ Arora KK Krsmanovic LZ Catt KJ 《Molecular endocrinology (Baltimore, Md.)》2003,17(12):1792-1804
Immortalized GnRH neurons (GT1-7) express receptors for estrogen [estrogen receptor-alpha and-13(ERa and ERI3)] and progesterone (progesterone receptor A) and exhibit positive immunostaining for both intracellular and plasma membrane ERs. Exposure of GT1-7 cells to picomolar estradiol concentrations for 5-60 min caused rapid, sustained,and dose-dependent inhibition of cAMP production. In contrast, treatment with nanomolar estradiol concentrations for 60 min increased cAMP production. The inhibitory and stimulatory actions of estradiol on cAMP formation were abolished by the ER antagonist, ICI 182,780. The estradiol-induced inhibition of cAMP production was prevented by treatment with pertussis toxin, consistent with coupling of the plasma membrane ER to an inhibitory G protein. Coimmunoprecipitation studies demonstrated an estradiol-regulated stimulatory interaction between ERa and G,3 that was prevented by the ER antagonist, ICI 182,780. Exposure of perifused GT1-7 cells and hypothalamic neurons to picomolar estradiol levels increased the GnRH peak interval, shortened peak duration, and increased peak amplitude. These findings indicate that occupancy of the plasma membrane-associated ERs expressed in GT1-7 neurons by physio-logical estradiol levels causes activation of a G, protein and modulates cAMP signaling and neuropeptide secretion. 相似文献