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261.
Heo KS Lee H Nigro P Thomas T Le NT Chang E McClain C Reinhart-King CA King MR Berk BC Fujiwara K Woo CH Abe J 《The Journal of cell biology》2011,193(5):867-884
Atherosclerosis is readily observed in regions of blood vessels where disturbed blood flow (d-flow) is known to occur. A positive correlation between protein kinase C ζ (PKCζ) activation and d-flow has been reported, but the exact role of d-flow-mediated PKCζ activation in atherosclerosis remains unclear. We tested the hypothesis that PKCζ activation by d-flow induces endothelial cell (EC) apoptosis by regulating p53. We found that d-flow-mediated peroxynitrite (ONOO(-)) increased PKCζ activation, which subsequently induced p53 SUMOylation, p53-Bcl-2 binding, and EC apoptosis. Both d-flow and ONOO(-) increased the association of PKCζ with protein inhibitor of activated STATy (PIASy) via the Siz/PIAS-RING domain (amino acids 301-410) of PIASy, and overexpression of this domain of PIASy disrupted the PKCζ-PIASy interaction and PKCζ-mediated p53 SUMOylation. En face confocal microscopy revealed increases in nonnuclear p53 expression, nitrotyrosine staining, and apoptosis in aortic EC located in d-flow areas in wild-type mice, but these effects were significantly decreased in p53(-/-) mice. We propose a novel mechanism for p53 SUMOylation mediated by the PKCζ-PIASy interaction during d-flow-mediated EC apoptosis, which has potential relevance to early events of atherosclerosis. 相似文献
262.
Sim FJ McClain CR Schanz SJ Protack TL Windrem MS Goldman SA 《Nature biotechnology》2011,29(10):934-941
Experimental animals with myelin disorders can be treated by transplanting oligodendrocyte progenitor cells (OPCs) into the affected brain or spinal cord. OPCs have been isolated by their expression of gangliosides recognized by mAb A2B5, but this marker also identifies lineage-restricted astrocytes and immature neurons. To establish a more efficient means of isolating myelinogenic OPCs, we sorted fetal human forebrain cells for CD140a, an epitope of platelet derived growth factor receptor (PDGFR)α, which is differentially expressed by OPCs. CD140a(+) cells were isolated as mitotic bipotential progenitors that initially expressed neither mature neuronal nor astrocytic phenotypic markers, yet could be instructed to either oligodendrocyte or astrocyte fate in vitro. Transplanted CD140a(+) cells were highly migratory and robustly myelinated the hypomyelinated shiverer mouse brain more rapidly and efficiently than did A2B5(+)cells. Microarray analysis of CD140a(+) cells revealed overexpression of the oligodendroglial marker CD9, suggesting that CD9(+)/CD140a(+) cells may constitute an even more highly enriched population of myelinogenic progenitor cells. 相似文献
263.
The 15N composition of the dominant form of dissolved inorganic nitrogen (DIN) was determined in upland groundwater, riparian groundwater, and stream water of the Barro Branco catchment, Amazônas, Brazil. The 15N composition of organic nitrogen in riparian and upland leaf litter was also determined. The data for these waters could be divided into three groups: upland groundwater DIN predominately composed of NO3
– with 15N values averaging 6.25 ± 0.9 riparian groundwater DIN primarily composed of NH4
+ with 15N values averaging 9.17 ± 1.0 and stream water DIN predominately composed of NO3
– with 15N values averaging 4.52 ± 0.8 Nitrate samples taken from the stream source and from the stream adjacent to the groundwater transects showed a downstream increase in 15N from 1.0to 4.5 Leaf litter samples averaged 3.5 ± 1.2The observed patterns in isotopic composition, together with previously observed inorganic nitrogen species and concentration shifts between upland, riparian and stream waters, suggest that groundwater DIN is not the primary source of DIN to the stream. Instead, the isotopic data suggest that remineralization of organic nitrogen within the stream itself may be a major source of stream DIN, and that the majority of DIN entering the stream via groundwater flowpaths is removed at the riparian-stream interface. 相似文献
264.
Molecular evolutionary dynamics of cytochrome b in strepsirrhine primates: the phylogenetic significance of third-position transversions 总被引:3,自引:2,他引:1
DNA sequences of the complete cytochrome b gene are shown to contain robust
phylogenetic signal for the strepsirrhine primates (i.e., lemurs and
lorises). The phylogeny derived from these data conforms to other molecular
studies of strepsirrhine relationships despite the fact that uncorrected
nucleotide distances are high for nearly all intrastrepsirrhine
comparisons, with most in the 15%-20% range. Cytochrome b sequences support
the hypothesis that Malagasy lemuriforms and Afro-Asian lorisiforms each
comprise clades that share a sister- group relationship. A study (Adkins
and Honeycutt 1994) of the cytochrome c oxidase subunit II (COII) gene
placed one Malagasy primate (Daubentonia) at the base of the strepsirrhine
clade, thereby suggesting a diphyletic Lemuriformes. The reanalysis of COII
third- position transversions, either alone or in combination with
cytochrome b third-position transversions, however, yields a tree that is
congruent with phylogenetic hypotheses derived from cytochrome b and other
genetic data sets.
相似文献
265.
Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis 总被引:1,自引:0,他引:1
Song Z Deaciuc I Zhou Z Song M Chen T Hill D McClain CJ 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(4):G894-G902
Although simple steatosis was originally thought to be a pathologically inert histological change, fat accumulation in the liver may play a critical role not only in disease initiation, but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Therefore, prevention of fat accumulation in the liver may be an effective therapy for multiple stages of nonalcoholic fatty liver disease (NAFLD). Promising beneficial effects of betaine supplementation on human NAFLD have been reported in some pilot clinical studies; however, data related to betaine therapy in NAFLD are limited. In this study, we examined the effects of betaine on fat accumulation in the liver induced by high-sucrose diet and evaluated mechanisms by which betaine could attenuate or prevent hepatic steatosis in this model. Male C57BL/6 mice weighing 20 +/- 0.5 g (means +/- SE) were divided into four groups (8 mice per group) and started on one of four treatments: standard diet (SD), SD+betaine, high-sucrose diet (HS), and HS + betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Long-term feeding of high-sucrose diet to mice caused significant hepatic steatosis accompanied by markedly increased lipogenic activity. Betaine significantly attenuated hepatic steatosis in this animal model, and this change was associated with increased activation of hepatic AMP-activated protein kinase (AMPK) and attenuated lipogenic capability (enzyme activities and gene expression) in the liver. Our findings are the first to suggest that betaine might serve as a therapeutic tool to attenuate hepatic steatosis by targeting the hepatic AMPK system. 相似文献
266.
Field validation of the MTI Actigraph and BodyMedia armband monitor using the IDEEA monitor 总被引:3,自引:0,他引:3
Objective: Accelerometers offer considerable promise for improving estimates of physical activity (PA) and energy expenditure (EE) in free‐living subjects. Differences in calibration equations and cut‐off points have made it difficult to determine the most accurate way to process these data. The objective of this study was to compare the accuracy of various calibration equations and algorithms that are currently used with the MTI Actigraph (MTI) and the Sensewear Pro II (SP2) armband monitor. Research Methods and Procedures: College‐age participants (n = 30) wore an MTI and an SP2 while participating in normal activities of daily living. Activity patterns were simultaneously monitored with the Intelligent Device for Estimating Energy Expenditure and Activity (IDEEA) monitor to provide an accurate estimate (criterion measure) of EE and PA for this field‐based method comparison study. Results: The EE estimates from various MTI equations varied considerably, with mean differences ranging from ?1.10 to 0.46 METS. The EE estimates from the two SP2 equations were within 0.10 METS of the value from the IDEEA. Estimates of time spent in PA from the MTI and SP2 ranged from 34.3 to 107.1 minutes per day, while the IDEEA yielded estimates of 52 minutes per day. Discussion: The lowest errors in estimation of time spent in PA and the highest correlations were found for the new SP2 equation and for the recently proposed MTI cut‐off point of 760 counts/min (Matthews, 2005). The study indicates that the Matthews MTI cut‐off point and the new SP2 equation provide the most accurate indicators of PA. 相似文献
267.
Huang J Gabrielsen JS Cooksey RC Luo B Boros LG Jones DL Jouihan HA Soesanto Y Knecht L Hazel MW Kushner JP McClain DA 《The Journal of biological chemistry》2007,282(52):37501-37507
Hereditary hemochromatosis is an inherited disorder of increased iron absorption that can result in cirrhosis, diabetes, and other morbidities. We have investigated the mechanisms underlying supranormal glucose tolerance despite decreased insulin secretion in a mouse model of hemochromatosis with deletion of the hemochromatosis gene (Hfe(-/-)). Hfe(-/-) mice on 129Sv or C57BL/6J backgrounds have decreased glucose excursions after challenge compared with controls. In the C57BL/6J/ Hfe(-/-), for example, incremental area under the glucose curve is reduced 52% (p < 0.001) despite decreased serum insulin, and homeostasis model assessment insulin resistance is decreased 50% (p < 0.05). When studied by the euglycemic clamp technique 129Sv/Hfe(-/-) mice exhibit a 20% increase in glucose disposal (p < 0.05) at submaximal insulin but no increase at maximal insulin compared with wild types. [1,2-(13)C]D-glucose clearance from plasma is significantly increased in Hfe(-/-) mice (19%, p < 0.05), and lactate derived from glycolysis is elevated 5.1-fold in Hfe(-/-) mice (p < 0.0001). Basal but not insulin-stimulated glucose uptake is elevated in isolated soleus muscle from Hfe(-/-) mice (p < 0.03). Compared with controls Hfe(-/-) mice exhibit no differences in serum lipid, insulin, glucagon, or thyroid hormone levels; adiponectin levels are elevated 41% (p < 0.05), and the adiponectin message in adipocytes is increased 83% (p = 0.04). Insulin action measured by phosphorylation of Akt is not enhanced in muscle, but phosphorylation of AMP-dependent kinase is increased. We conclude that supranormal glucose tolerance in iron overload is characterized by increased glucose disposal that does not result from increased insulin action. Instead, the Hfe(-/-) mice demonstrate increased adiponectin levels and activation of AMP-dependent kinase. 相似文献
268.
C J McClain D A Cohen C A Dinarello J G Cannon S I Shedlofsky A M Kaplan 《Life sciences》1986,39(16):1479-1485
Interleukin-1 (IL-1) is a monokine which has been demonstrated to produce a variety of seemingly diverse metabolic events including fever, neutrophilia, anorexia, altered mineral metabolism, muscle catabolism, and fibroblast proliferation. Because many of the clinical features of alcoholic hepatitis are metabolic abnormalities that have been shown to be caused by IL-1, we questioned whether patients with alcoholic hepatitis had elevated serum levels of IL-1. Six patients with alcoholic hepatitis had serum IL-1 activity measured by the thymocyte costimulator assay after serum inhibitors were removed. Their values were compared to those of 6 age and sex-matched healthy controls. Patients with alcoholic hepatitis had markedly elevated serum IL-1 activity, with the integrated value of all fractions having serum IL-1 activity being 9.8 times that of controls. IL-1 activity in serum from alcoholic hepatitis patients also was blocked by antibody to IL-1. We conclude that patients with alcoholic hepatitis have increased serum IL-1 activity which may play a role in certain of the metabolic complications of alcoholic hepatitis. 相似文献
269.
270.
David E. McClain Mildred A. Donlon Stephen Chock George N. Catravas 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1983,763(4):419-425
To investigate the role of the Ca2+-binding protein calmodulin on histamine release in the rat peritoneal mast cell, we exposed cells to exogenous calmodulin in the presence of a variety of histamine secretagogues. Histamine release stimulated by compound
, polymyxin B and ionophore A23187 was inhibited while concanavalin A-stimulated release was not affected. Calmodulin in the presence of the secretagogues did not affect cell viability and calmodulin alone had no effect on histamine release. No direct interaction between calmodulin and the secretagogues was observed. Exogenous calmodulin does not appear to be incorporated into the cell. The inhibition of histamine release by calmodulin can be explained as a labile interaction between the protein and the cell that requires externally-bound Ca2+. These experiments demonstrate the use of exogenous calmodulin as a probe in the study of the mechanism of histamine release. 相似文献