排序方式: 共有21条查询结果,搜索用时 125 毫秒
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Wong Dorothy Plumb James Talab Hosamiddine Kurdi Mouhamad Pokhrel Keshav Oelkers Peter 《Mycopathologia》2019,184(2):213-226
Mycopathologia - Perturbing ergosterol synthesis has been previously shown to reduce the virulence of Candida albicans. We tested the hypothesis that further altering cell membrane composition by... 相似文献
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p38-mediated regulation of an Fas-associated death domain protein-independent pathway leading to caspase-8 activation during TGFbeta-induced apoptosis in human Burkitt lymphoma B cells BL41 下载免费PDF全文
Schrantz N Bourgeade MF Mouhamad S Leca G Sharma S Vazquez A 《Molecular biology of the cell》2001,12(10):3139-3151
On binding to its receptor, transforming growth factor beta (TGFbeta) induces apoptosis in a variety of cells, including human B lymphocytes. We have previously reported that TGFbeta-mediated apoptosis is caspase-dependent and associated with activation of caspase-3. We show here that caspase-8 inhibitors strongly decrease TGFbeta-mediated apoptosis in BL41 Burkitt's lymphoma cells. These inhibitors act upstream of the mitochondria because they inhibited the loss of mitochondrial membrane potential observed in TGFbeta-treated cells. TGFbeta induced caspase-8 activation in these cells as shown by the cleavage of specific substrates, including Bid, and the appearance of cleaved fragments of caspase-8. Our data show that TGFbeta induces an apoptotic pathway involving sequential caspase-8 activation, loss of mitochondrial membrane potential, and caspase-9 and -3 activation. Caspase-8 activation was Fas-associated death domain protein (FADD)-independent because cells expressing a dominant negative mutant of FADD were still sensitive to TGFbeta-induced caspase-8 activation and apoptosis. This FADD-independent pathway of caspase-8 activation is regulated by p38. Indeed, TGFbeta-induced activation of p38 and two different inhibitors specific for this mitogen-activated protein kinase pathway (SB203580 and PD169316) prevented TGFbeta-mediated caspase-8 activation as well as the loss of mitochondrial membrane potential and apoptosis. Overall, our data show that p38 activation by TGFbeta induced an apoptotic pathway via FADD-independent activation of caspase-8. 相似文献
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Phosphoprotein enriched in astrocytes-15 kDa expression inhibits astrocyte migration by a protein kinase C delta-dependent mechanism 下载免费PDF全文
Renault-Mihara F Beuvon F Iturrioz X Canton B De Bouard S Léonard N Mouhamad S Sharif A Ramos JW Junier MP Chneiweiss H 《Molecular biology of the cell》2006,17(12):5141-5152
Phosphoprotein enriched in astrocytes-15 kDa (PEA-15), a phosphoprotein enriched in astrocytes, inhibits both apoptosis and proliferation in normal and cancerous cells. Here, analysis of PEA-15 expression in glioblastoma organotypic cultures revealed low levels of PEA-15 in tumor cells migrating away from the explants, regardless of the expression levels in the originating explants. Because glioblastomas are highly invasive primary brain tumors that can originate from astrocytes, we explored the involvement of PEA-15 in the control of astrocyte migration. PEA-15-/- astrocytes presented an enhanced motility in vitro compared with their wild-type counterparts. Accordingly, NIH-3T3 cells transfected by green fluorescent protein-PEA-15 displayed a reduced migration. Reexpression of PEA-15 restored PEA-15-/- astrocyte motility to wild-type levels. Pharmacological manipulations excluded a participation of extracellular signal-regulated kinase/mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt, and calcium/calmodulin-dependent protein kinase II in this effect of PEA-15. In contrast, treatment by bisindolylmaleimide, G?6976, and rottlerin, and chronic application of phorbol 12-myristate 13-acetate and/or bryostatin-1 indicated that PKC delta mediated PEA-15 inhibition of astrocyte migration. PEA-15-/- astrocytes constitutively expressed a 40-kDa form of PKC delta that was down-regulated upon PEA-15 reexpression. Together, these data reveal a new function for PEA-15 in the inhibitory control of astrocyte motility through a PKC delta-dependent pathway involving the constitutive expression of a catalytic fragment of PKC delta. 相似文献
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A chemical inhibitor of Apaf-1 exerts mitochondrioprotective functions and interferes with the intra-S-phase DNA damage checkpoint 总被引:1,自引:0,他引:1
Laura Mondragón Lorenzo Galluzzi Shahul Mouhamad Mar Orzáez José-Miguel Vicencio Ilio Vitale Alejandra Moure Angel Messeguer Enrique Perez-Paya Guido Kroemer 《Apoptosis : an international journal on programmed cell death》2009,14(2):182-190
QM31 represents a new class of cytoprotective agents that inhibit the formation of the apoptosome, the caspase activation
complex composed by Apaf-1, cytochrome c, dATP and caspase-9. Here, we analyzed the cellular effects of QM31, as compared to the prototypic caspase inhibitor Z-VAD-fmk.
QM31 was as efficient as Z-VAD-fmk in suppressing caspase-3 activation, and conferred a similar cytoprotective effect. In
contrast to Z-VAD-fmk, QM31 inhibited the release of cytochrome c from mitochondria, an unforeseen property that may contribute to its pronounced cytoprotective activity. Moreover, QM31 suppressed
the Apaf-1-dependent intra-S-phase DNA damage checkpoint. These results suggest that QM31 can interfere with the two known
functions of Apaf-1, namely apoptosome assembly/activation and intra-S-phase cell cycle arrest. Moreover, QM31 can inhibit
mitochondrial outer membrane permeabilization, an effect that is independent from its action on Apaf-1. 相似文献
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Zachary P Neeb Jason M Edwards Mouhamad Alloosh Xin Long Eric A Mokelke Michael Sturek 《Comparative medicine》2010,60(4):300-315
Metabolic syndrome (MetS), a compilation of associated risk factors, increases the risk of type 2 diabetes and coronary artery disease (CAD, atherosclerosis), which can progress to the point of artery occlusion. Stents are the primary interventional treatment for occlusive CAD, and patients with MetS and hyperinsulinemia have increased restenosis. Because of its thrifty genotype, the Ossabaw pig is a model of MetS. We tested the hypothesis that, when fed high-fat diet, Ossabaw swine develop more features of MetS, greater native CAD, and greater stent-induced CAD than do Yucatan swine. Animals of each breed were divided randomly into 2 groups and fed 2 different calorie-matched diets for 40 wk: control diet (C) and high-fat, high-cholesterol atherogenic diet (H). A bare metal stent was placed in the circumflex artery, and pigs were allowed to recover for 3 wk. Characteristics of MetS, macrovascular and microvascular CAD, in-stent stenosis, and Ca2+ signaling in coronary smooth muscle cells were evaluated. MetS characteristics including, obesity, glucose intolerance, hyperinsulinemia, and elevated arterial pressure were elevated in Ossabaw swine compared to Yucatan swine. Ossabaw swine with MetS had more extensive and diffuse native CAD and in-stent stenosis and impaired coronary blood flow regulation compared with Yucatan. In-stent atherosclerotic lesions in Ossabaw coronary arteries were less fibrous and more cellular. Coronary smooth muscle cells from Ossabaw had impaired Ca2+ efflux and intracellular sequestration versus cells from Yucatan swine. Therefore, Ossabaw swine are a superior model of MetS, subsequent CAD, and cellular Ca2+ signaling defects, whereas Yucatan swine are leaner and relatively resistant to MetS and CAD.Abbreviations: CAD, coronary artery disease; CSM, coronary smooth muscle; IVGTT, intravenous glucose tolerance test; MetS, metabolic syndrome; SERCA, sarco–endoplasmic reticulum Ca2+ ATPase; ET1, endothelin 1; SOCE, store-operated Ca2+ entryAtherosclerotic coronary artery disease (CAD) is increased at least 2-fold in patients with metabolic syndrome (MetS)27 and is accompanied by marked microvascular dysfunction that further impairs coronary blood flow.10 MetS generally is diagnosed by the presence of 3 or more of the following conditions: obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension.17,28 There is strong support for the role of the hyperinsulinemia component of MetS in increased restenosis after percutaneous coronary interventions.74,75,84,85 Further, our group has shown that severe coronary microvascular dysfunction occurs in MetS.5 Because MetS (so-called ‘prediabetes’) affects as much as 27% of the United States population, is increasing dramatically in prevalence,94 and can progress to type 2 diabetes, there is great need for basic research using animal models that accurately mimic MetS and the accompanying CAD. Clearly, there is need for study of MetS-induced CAD and in-stent stenosis and the underlying cellular and molecular mechanisms.Mice, rats, and swine are known to recapitulate MetS;3,12,36,60,71,72 however, none of these models fully reproduce the combined symptoms of MetS and CAD. Further, transgenic mouse models are simply not adequate for coronary vascular interventions using stents identical to those used in humans,18,23,38,55,57,79,83,86 a step that is essential for translation to the clinic. Yucatan and domestic swine are commonly used large animal models for study of cardiovascular disease due to their ability to mimic the neointimal formation and thrombosis observed in humans.86 For example, several laboratories have produced severe CAD in swine,8,24,51,61,62,68,91 but through toxin-induced pancreatic β-cell ablation and feeding of an atherogenic diet, rather than as a natural development subsequent to MetS or diabetes. Currently, there is a paucity of large animal models that reproduce MetS and CAD.3Research on the obesity-prone Ossabaw miniature swine59 clearly indicates that these animals develop MetS and cardiovascular disease when fed a high-calorie atherogenic diet,4,5,9,16,19,42,50,52,83,92 Female Ossabaw swine on this type of diet nearly doubled their percentage body fat in only 9 wk, showed insulin resistance, impaired glucose tolerance, dyslipidemia (profound increase in the ratio of low-density to high-density lipoprotein cholesterol, hypertriglyceridemia), hypertension, and early coronary atherosclerosis.16 These data contrast with those from male Yucatan miniature pigs, which did not develop MetS even after 20 wk on a comparable excess calorie atherogenic diet.8,68,95 Yucatan swine do not develop MetS through diet manipulation, unlike Ossabaw swine, which consistently recapitulate all MetS characteristics. However, important differences in study design have not allowed direct comparison between Yucatan and Ossabaw swine.Cytosolic Ca2+ signaling is involved in ‘phenotypic modulation’ of coronary smooth muscle (CSM), as characterized by proliferation and migration in several in vitro cell culture models33,35,89,90 and in vivo rodent models of the peripheral circulation (for example, reference 51). The Yucatan swine model of diabetic dyslipidemia shows altered Ca2+ extrusion,96 Ca2+ sequestration by the sarcoplasmic reticulum,32,34,98 and Ca2+ influx through voltage-gated Ca2+ channels.98 Currently, Ca2+ signaling has not been compared directly between MetS Ossabaw and Yucatan swine CSM. Therefore, the purpose of the present study was to test the hypothesis that compared with Yucatan swine on calorie-matched standard chow (for example, Yucatan maintenance diet8,95) and atherogenic diets, Ossabaw swine have a greater propensity to MetS and CAD with impaired coronary microvascular dysfunction and Ca2+ handling in CSM. 相似文献
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Fengyu Xie Mouhamad Said Diallo Haegyeom Kim Qingsong Howard Tu Gerbrand Ceder 《Liver Transplantation》2024,14(10):2302960
Lithium metal solid-state batteries (LMSSBs) have demonstrated their high energy density and cycling performance at high current densities in an anode-free architecture, featuring a thin Ag/C composite buffer layer (BL) between the current collector (CC) and the solid electrolyte (SE). This study explains the microscopic mechanism of the Ag/C BL by using first-principles atomistic and continuum modeling. It is shown that Ag effectively acts as a homogeneous solid-solution beyond AgLi2.32 and maintains a positive potential even at AgLi25 during lithiation. Key factors underlying the working of the Ag/C BL include lower interfacial resistance at the BL/CC interface than at the BL/SE interface, leading to predominant Li deposition on BL/CC, and substantial Ag–Li volume expansion during lithiation. This, combined with stronger BL/SE adhesion, causes BL/SE separation and Ag–Li extrusion toward the CC side. During delithiation, Ag re-precipitates as nanoparticles uniformly on the CC, with its positive lithiation potential homogenizing Li currents in subsequent cycles. Other metals are less effective due to their relatively large overpotential, premature lithiation termination, and limited volume expansions hindering movement toward the CC. The study aids the BL design, focusing on metal choice and optimization material and microstructural properties, such as the Li-ion conductivity and interfacial resistance. 相似文献