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1.
Brizuela L Rábano M Peña A Gangoiti P Macarulla JM Trueba M Gómez-Muñoz A 《Journal of lipid research》2006,47(6):1238-1249
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid capable of regulating critical physiological and pathological functions. Here, we report for the first time that S1P stimulates aldosterone secretion in cells of the zona glomerulosa of the adrenal gland. Regulation of aldosterone secretion is important because this hormone controls electrolyte and fluid balance and is implicated in cardiovascular homeostasis. S1P-stimulated aldosterone secretion was dependent upon the protein kinase C (PKC) isoforms alpha and delta and extracellular Ca2+, and it was inhibited by pertussis toxin (PTX). S1P activated phospholipase D (PLD) through a PTX-sensitive mechanism, also involving PKC alpha and delta and extracellular Ca2+. Primary alcohols, which attenuate the formation of phosphatidic acid (the product of PLD), and cell-permeable ceramides, which inhibit PLD activity, blocked S1P-stimulated aldosterone secretion. Furthermore, propranolol, chlorpromazine, and sphingosine, which are potent inhibitors of phosphatidate phosphohydrolase (PAP) (the enzyme that produces diacylglycerol from phosphatidate), also blocked aldosterone secretion. These data suggest that the PLD/PAP pathway plays a crucial role in the regulation of aldosterone secretion by S1P and that Gi protein-coupled receptors, extracellular Ca2+, and the PKC isoforms alpha and delta are all important components in the cascade of events controlling this process. 相似文献
2.
Yanqin Ren Szu Han Huang Amanda B. Macedo Adam R. Ward Winiffer D. Conce Alberto Thais Klevorn Louise Leyre Dennis C. Copertino Talia M. Mota Dora Chan Ronald Truong Thomas Rohwetter Paul Zumbo Friederike Dündar Doron Betel Colin Kovacs Erika Benko Alberto Bosque R. Brad Jones 《Journal of virology》2021,95(15)
3.
As part of a program to select maritime pine (Pinus pinaster Ait.) genotypes for resistance to low winter temperatures, we examined variation in photosystem II activity by chlorophyll fluorescence. Populations and families within populations from contrasting climates were tested during two consecutive winters through two progeny trials, one located at a continental and xeric site and one at a mesic site with Atlantic influence. We also obtained the LT50, or the temperature that causes 50% damage, by controlled freezing and the subsequent analysis of chlorophyll fluorescence in needles and stems that were collected from populations at the continental trial site.
P. pinaster showed sensitivity to winter stress at the continental site, during the colder winter. The combination of low temperatures, high solar irradiation and low precipitation caused sustained decreases in maximal photochemical efficiency (Fv/Fm), quantum yield of non-cyclic electron transport (ΦPSII) and photochemical quenching (qP). The variation in photochemical parameters was larger among families than among populations, and population differences appeared only under the harshest conditions at the continental site. As expected, the environmental effects (winter and site) on the photochemical parameters were much larger than the genotypic effects (population or family). LT50 was closely related to the minimum winter temperatures of the population''s range. The dark-adapted Fv/Fm ratio discriminated clearly between interior and coastal populations.In conclusion, variations in Fv/Fm, ΦPSII, qP and non-photochemical quenching (NPQ) in response to winter stress were primarily due to the differences between the winter conditions and the sites and secondarily due to the differences among families and their interactions with the environment. Populations from continental climates showed higher frost tolerance (LT50) than coastal populations that typically experience mild winters. Therefore, LT50, as estimated by Fv/Fm, is a reliable indicator of frost tolerance among P. pinaster populations. 相似文献
4.
Domínguez JM Fuertes A Orozco L del Monte-Millán M Delgado E Medina M 《The Journal of biological chemistry》2012,287(2):893-904
Tideglusib is a GSK-3 inhibitor currently in phase II clinical trials for the treatment of Alzheimer disease and progressive supranuclear palsy. Sustained oral administration of the compound to a variety of animal models decreases Tau hyperphosphorylation, lowers brain amyloid plaque load, improves learning and memory, and prevents neuronal loss. We report here that tideglusib inhibits GSK-3β irreversibly, as demonstrated by the lack of recovery in enzyme function after the unbound drug has been removed from the reaction medium and the fact that its dissociation rate constant is non-significantly different from zero. Such irreversibility may explain the non-competitive inhibition pattern with respect to ATP shown by tideglusib and perhaps other structurally related compounds. The replacement of Cys-199 by an Ala residue in the enzyme seems to increase the dissociation rate, although the drug retains its inhibitory activity with decreased potency and long residence time. In addition, tideglusib failed to inhibit a series of kinases that contain a Cys homologous to Cys-199 in their active site, suggesting that its inhibition of GSK-3β obeys to a specific mechanism and is not a consequence of nonspecific reactivity. Results obtained with [(35)S]tideglusib do not support unequivocally the existence of a covalent bond between the drug and GSK-3β. The irreversibility of the inhibition and the very low protein turnover rate observed for the enzyme are particularly relevant from a pharmacological perspective and could have significant implications on its therapeutic potential. 相似文献
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6.
Séverin S Pollitt AY Navarro-Nuñez L Nash CA Mourão-Sá D Eble JA Senis YA Watson SP 《The Journal of biological chemistry》2011,286(6):4107-4116
The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors. 相似文献
7.
Olatz Arteaga Miren Revuelta Leyre Urigüen Antonia álvarez Haizea Montalvo Enrique Hilario 《PloS one》2015,10(11)
Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia. 相似文献
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9.
José Luis Barrios Andrés Leyre Mónica López-Soria Ana Alastruey Izquierdo Jaime Echevarría Ecenarro Raquel Feijoó Lera Jesus Garrido Fierro Francisco Javier Cabrerizo Nuñez Andrés Canut Blasco 《Revista iberoamericana de micología》2018,35(2):92-96
Background
Although fortunately very rare in countries with a temperate climate, certain factors, such as clinical or pharmacological immunosuppression, may cause Fusarium-related fungal infections to become an emerging problem. Moreover, Fusarium is one of the most important etiological agents in exogenous endophthalmitis, which is often favored by the disruption of the epithelial barriers.Aims
The aim of this series of clinical cases is to identify characteristic clinical findings that may allow an early diagnosis and more efficient management of this ophthalmologic emergency.Methods
Three cases of endophthalmitis due to Fusarium solani and Fusarium oxysporum, diagnosed in 2009, 2010, and 2014 in patients from two different health regions belonging to the same health system and separated by around 43 miles, are presented. The Fusarium isolates were initially identified microscopically and the species subsequently confirmed by sequencing the elongation factor alpha (EFα) and internal transcribed spacers (ITS). Susceptibility to antifungal agents was determined using the EUCAST broth dilution method.Results
Evolution was poor as two of the three patients progressed to phthisis bulbi despite surgical measures and broad-spectrum antifungal antibiotic therapy.Conclusions
It is essential to rapidly instigate multidisciplinary measures to combat suspected endophthalmitis due to Fusarium given the poor prognosis of this type of infection. 相似文献10.
Radial-growth and wood-anatomical changes in overaged Quercus pyrenaica coppice stands: functional responses in a new Mediterranean landscape 总被引:1,自引:1,他引:0
Leyre Corcuera J. Julio Camarero Sergio Sisó Eustaquio Gil-Pelegrín 《Trees - Structure and Function》2006,20(1):91-98
Recent land-use changes in intensively managed forests such as Mediterranean coppice stands might profoundly alter their structure
and function. We assessed how the abandonment of traditional management practices in coppice stands, which consisted of short
cutting-cycles (10–15 years), has caused overaging (stems are usually much older than when they were coppiced) and altered
their wood anatomy and hydraulic architecture. We studied the recent changes of wood anatomy, radial growth, and hydraulic
architecture in two stands of Quercus pyrenaica, a transitional Mediterranean oak with ring-porous wood forming coppice stands in W–NW Spain. We selected a xeric and a mesic
site because of their contrasting climates and disturbance histories. The xeric site experienced an intense defoliation after
the severe 1993–1994 summer drought. The mesic site was thinned in late 1994. We studied the temporal variability in width,
vessel number and diameter, and predicted the hydraulic conductivities (K
h) of earlywood and latewood. In the mesic site, we estimated the vulnerability to xylem cavitation of earlywood vessels. Overaging
caused a steep decline in latewood production at a cambial age of 14 years., which was close to the customary cutting cycle
of Q. pyrenaica. The diameter distribution of vessels was bimodal, and latewood vessels only accounted for 4% of the K
h. Overaging, acting as a predisposing factor in the decline episode, was observed at the xeric site, where most trees did
not produce latewood in 1993–1995. At the mesic site, thinned trees formed wider tree-rings, more latewood and multiseriate
tree-rings than overaged trees. The growth enhancement remained 8 years after thinning. Most of the hydraulic conductivity
in earlywood was lost in a narrow range of potentials, between −2.5 and −3.5 MPa. We have shown how hydraulic conductivity
and radial growth are closely related in Q. pyrenaica and how aging modulates this relationship. 相似文献