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11.
Cholesterol modulates vascular reactivity to endothelin-1 by stimulating a pro-inflammatory pathway 总被引:9,自引:0,他引:9
Paris D Town T Humphrey J Yokota K Mullan M 《Biochemical and biophysical research communications》2000,274(2):553-558
Hypercholesterolemia (HC) is associated with coronary endothelial dysfunction and increased circulating levels of endothelin-1. We show that pre-treatment of intact rat aortic rings with cholesterol synergistically enhances the vasoconstriction induced by endothelin-1 suggesting that elevated levels of cholesterol may predispose to hypertension by modulating the vascular reactivity to endogenous vasoconstrictors. Moreover, we report that SB202190, a selective inhibitor of p38 MAPK, and PD98059 an inhibitor of MEK1/2 are able to abolish the vasoactive properties of cholesterol. MK-886, an inhibitor of 5-lipoxygenase is inefficient at blocking the vasoactive properties of cholesterol whereas NS-398, a selective inhibitor of cyclooxygenase-2 (COX-2) completely abolishes cholesterol-induced vasoconstriction. In intact rat aortae, cholesterol stimulates prostaglandin E(2) and prostaglandin F(2 alpha) production, an effect that can be completely prevented by inhibiting p38 MAPK, or COX-2. In vitro, cholesterol appears to stimulate a similar pro-inflammatory pathway in human cerebrovascular smooth muscle cells. Disruption of the MAPK/COX-2 pathway may represent a valuable therapy to block the hypertension associated with HC, as well as the development of atherosclerosis. 相似文献
12.
Ellen M Moran Ronan Mullan Jennifer McCormick Mary Connolly Owen Sullivan Oliver FitzGerald Barry Bresnihan Douglas J Veale Ursula Fearon 《Arthritis research & therapy》2009,11(4):R113-12
Introduction
The aim of this study was to examine IL-17A in patients, following anti-TNF-α therapy and the effect of IL-17A on matrix turnover and cartilage degradation. 相似文献13.
David L. Kimbro Edwin D. Grosholz Adam J. Baukus Nicholas J. Nesbitt Nicole M. Travis Sarikka Attoe Caitlin Coleman-Hulbert 《Oecologia》2009,160(3):563-575
Although invasive species often resemble their native counterparts, differences in their foraging and anti-predator strategies
may disrupt native food webs. In a California estuary, we showed that regions dominated by native crabs and native whelks
have low mortality of native oysters (the basal prey), while regions dominated by invasive crabs and invasive whelks have
high oyster mortality and are consequently losing a biologically diverse habitat. Using field experiments, we demonstrated
that the invasive whelk’s distribution is causally related to a large-scale pattern of oyster mortality. To determine whether
predator–prey interactions between crabs (top predators) and whelks (intermediate consumers) indirectly control the pattern
of oyster mortality, we manipulated the presence and invasion status of the intermediate and top trophic levels in laboratory
mesocosms. Our results show that native crabs indirectly maintain a portion of the estuary’s oyster habitat by both consuming
native whelks (density-mediated trophic cascade) and altering their foraging behavior (trait-mediated trophic cascade). In
contrast, invasive whelks are naive to crab predators and fail to avoid them, thereby inhibiting trait-mediated cascades and
their invasion into areas with native crabs. Similarly, when native crabs are replaced with invasive crabs, the naive foraging
strategy and smaller size of invasive crabs prevents them from efficiently consuming adult whelks, thereby inhibiting strong
density-mediated cascades. Thus, while trophic cascades allow native crabs, whelks, and oysters to locally co-exist, the replacement
of native crabs and whelks by functionally similar invasive species results in severe depletion of native oysters. As coastal
systems become increasingly invaded, the mismatch of evolutionarily based strategies among predators and prey may lead to
further losses of critical habitat that support marine biodiversity and ecosystem function.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
14.
The incubation of beta-carotene-(14)C with the soluble fraction of the intestinal mucosa resulted in the formation of small amounts of acidic material. The addition of NAD or NADH to the soluble fraction caused a tenfold increase in this material. Incubation of retinal-15-(14)C with the soluble fraction of the intestinal mucosa plus NAD or NADH resulted in the conversion of 80-90% of the retinal to acidic material, which has been shown to contain retinoic acid. In vivo studies on the formation of retinoic acid in the intestinal mucosa after the administration of beta-carotene-(14)C revealed that an appreciable amount of beta-carotene was converted to acidic compounds. When retinal-15-(14)C was administered, portal blood contained 30-40% of the absorbed radioactivity. 24% of this radioactivity was found in acidic material, which has been shown to contain retinoic acid. It is suggested that enzymes in rat intestine cleave beta-carotene to retinal and oxidize the latter to retinoic acid, which is then transported via the portal circulation to the liver. 相似文献
15.
Circulation and turnover of synaptic vesicle membrane in cultured fetal mammalian spinal cord neurons 总被引:2,自引:9,他引:2 下载免费PDF全文
Intact neurons in cultures of fetal rodent spinal cord explants show stimulation-dependent uptake of horseradish peroxidase (HRP) into many small vesicles and occasional tubules and multivesicular bodies (MVB) at presynaptic terminals. Presynaptic terminals were allowed to take up HRP during 1 h of strychnine-enhanced stimulation of synaptic transmitter release and then "chased" in tracer-free medium either with strychnine or with 10 mM Mg++ which depresses transmitter release. Tracer-containing vesicles are lost from terminals under both chase conditions; the loss is more rapid (4-8 h) with strychnine than with 10 mM Mg++ (8-16 h). There is a parallel decrease in the numbers of labeled MVB's at terminals. Loss of tracer with 10 mM Mg++ does not appear to be due to the membrane rearrangements (exocytosis coupled to endocytosis) that presumably lead to initial tracer uptake; terminals exposed to HRP and Mg++ for up to 16 h show little tracer uptake into vesicles. Nor is the decrease likely to the due to loss of HRP enzyme activity; HRP is very stable in solution. During the chases there is a striking accumulation of HRP in perikarya that is far more extensive in cultures initially exposed to tracer with strychnine than 10 mM Mg++ regardless of chase conditions. Much of the tracer ends up in large dense bodies. These findings suggest that synaptic vesicle membrane turnover involves retrograde axonal transport of membrane to neuronal perikarya for further processing, including lysosomal degradation. The more rapid (4-8 h) loss of tracer-containing vesicles with strychnine may reflect vesicle membrane reutilization for exocytosis. 相似文献
16.
17.
Jacob Holechek Robert Lease Ann-Gerd Thorsell Tobias Karlberg Caitlin McCadden Ryan Grant Abby Keen Evan Callahan Herwig Schüler Dana Ferraris 《Bioorganic & medicinal chemistry letters》2018,28(11):2050-2054
A series of diaryl ethers were designed and synthesized to discern the structure activity relationships against the two closely related mono-(ADP-ribosyl)transferases PARP10 and PARP14. Structure activity studies identified 8b as a sub-micromolar inhibitor of PARP10 with?~15-fold selectivity over PARP14. In addition, 8k and 8m were discovered to have sub-micromolar potency against PARP14 and demonstrated moderate selectivity over PARP10. A crystal structure of the complex of PARP14 and 8b shows binding of the compound in a novel hydrophobic pocket and explains both potency and selectivity over other PARP family members. In addition, 8b, 8k and 8m also demonstrate selectivity over PARP1. Together, this study identified novel, potent and metabolically stable derivatives to use as chemical probes for these biologically interesting therapeutic targets. 相似文献
18.
Graeme T. Swindles Paul J. Morris Bronwen Whitney Jennifer M. Galloway Mariusz Gałka Angela Gallego‐Sala Andrew L. Macumber Donal Mullan Mark W. Smith Matthew J. Amesbury Thomas P. Roland Hamed Sanei R. Timothy Patterson Nicole Sanderson Lauren Parry Dan J. Charman Omar Lopez Elvis Valderamma Elizabeth J. Watson Ruza F. Ivanovic Paul J. Valdes T. Edward Turner Outi Lähteenoja 《Global Change Biology》2018,24(2):738-757
The most carbon (C)‐dense ecosystems of Amazonia are areas characterized by the presence of peatlands. However, Amazonian peatland ecosystems are poorly understood and are threatened by human activities. Here, we present an investigation into long‐term ecohydrological controls on C accumulation in an Amazonian peat dome. This site is the oldest peatland yet discovered in Amazonia (peat initiation ca. 8.9 ka BP), and developed in three stages: (i) peat initiated in an abandoned river channel with open water and aquatic plants; (ii) inundated forest swamp; and (iii) raised peat dome (since ca. 3.9 ka BP). Local burning occurred at least three times in the past 4,500 years. Two phases of particularly rapid C accumulation (ca. 6.6–6.1 and ca. 4.9–3.9 ka BP), potentially resulting from increased net primary productivity, were seemingly driven by drier conditions associated with widespread drought events. The association of drought phases with major ecosystem state shifts (open water wetland–forest swamp–peat dome) suggests a potential climatic control on the developmental trajectory of this tropical peatland. A third drought phase centred on ca. 1.8–1.1 ka BP led to markedly reduced C accumulation and potentially a hiatus during the peat dome stage. Our results suggest that future droughts may lead to phases of rapid C accumulation in some inundated tropical peat swamps, although this can lead ultimately to a shift to ombrotrophy and a subsequent return to slower C accumulation. Conversely, in ombrotrophic peat domes, droughts may lead to reduced C accumulation or even net loss of peat. Increased surface wetness at our site in recent decades may reflect a shift towards a wetter climate in western Amazonia. Amazonian peatlands represent important carbon stores and habitats, and are important archives of past climatic and ecological information. They should form key foci for conservation efforts. 相似文献
19.
20.
<Emphasis Type="Italic">Vespula germanica</Emphasis> Foragers Do Not Scent-Mark Carbohydrate Food Sites 总被引:2,自引:0,他引:2
Jennifer?M.?Jandt Laura?Riel Benjamin?Crain Robert?L.?JeanneEmail author 《Journal of Insect Behavior》2005,18(1):19-31
We tested whether foragers of Vespula germanica leave a chemical attractant at a carbohydrate food site. Foragers were allowed to make 50 or 100 visits to a feeder filled with a rich, unscented fructose solution. We then gave them a choice between this and an identical but unvisited feeder. There was no difference between the number of individuals that chose the visited feeder and those that chose the unvisited one. Instead, wasps showed a tendency to choose a feeder based on its relative position on the feeding stand. We conclude that foragers of V. germanica do not scent-mark food sites. Instead, in the absence of food odor, they rely on local visual cues to relocate carbohydrate food sources. 相似文献