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排序方式: 共有120条查询结果,搜索用时 734 毫秒
61.
62.
Placental vascular malformations result in fetal hypoxia, a serious pregnancy complication. Recent studies have linked liver-secreted and hemostatic proteins with angiogenesis. We therefore evaluated liver protein secretion changes following hypoxia, and their effect on angiogenesis, to identify potential angiogenic protein changes in the plasma of hypoxic newborns. Human vascular endothelial cells exhibited 10-fold increased tube formation with secretions from HepG2 cells cultured in 1% O(2) and 3-fold in 4% O(2) (p < 0.0001, p < 0.05) compared to 20% O(2). 2-DGE profiling of the secretions revealed significant density changes (p < 0.05) in spots identified as angiogenic proteins by LC-MS/MS. Clusterin decreased (-1.6-fold), whereas two spots of plasminogen activator inhibitor-1 (PAI-1) (2.4, and 3.6-fold), and three spots of transferrin (1.3, 1.5, and 2.6-fold) increased with 1% O(2). The levels of these proteins, subsequently determined in fetal plasma by immunoassays, strongly correlate with the fetal blood oxygen level at birth; PAI-1 and transferrin increase with low venous pO(2) (r = -0.70, p = 0.02, and r = -0.66, p = 0.04), clusterin and fibrinogen decrease (r = 0.82, p = 0.002, and r = 0.70, p = 0.02). These findings demonstrate that low oxygen levels in utero lead to pro-angiogenic changes in liver secreted plasma proteins. The pro-vascular plasma environment in hypoxic pregnancies may be acting to mitigate the compromised vasculature. 相似文献
63.
Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; P<0.001), increased superoxide and secondary ROS/RNS generation along with oxidative damage to cellular macromolecules. Nimesulide reduced mitochondrial activity, depolarized mitochondria and caused membrane permeability transition (MPT) followed by release of apoptotic proteins (AIF; apoptosis inducing factor, EndoG; endonuclease G, and Cyto c; cytochrome c). It also significantly activated caspase-9 and caspase-3 and increased oxidative DNA damage (level of 8-Oxoguanine glycosylase; P<0.05). A combination of camphene and geraniol (CG; 1:1), when pre-administered in rats (10 mg/kg BW), accorded protection against nimesulide hepatotoxicity in vivo, as evident from normalized serum biomarkers and histopathology. mRNA expression and activity of key antioxidant and redox enzymes along with oxidative stress were also normalized due to CG pre-treatment. Downstream effects like decreased mitochondrial swelling, inhibition in release of apoptotic proteins, prevention of mitochondrial depolarization along with reduction in oxidized NAD(P)H and increased mitochondrial electron flow further supported protective action of selected terpenes against nimesulide toxicity. Therefore CG, a combination of natural terpenes prevented nimesulide induced cellular damage and ensuing hepatotoxicity. 相似文献
64.
Gilmore SA Schelle MW Holsclaw CM Leigh CD Jain M Cox JS Leary JA Bertozzi CR 《ACS chemical biology》2012,7(5):863-870
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a highly evolved human pathogen characterized by its formidable cell wall. Many unique lipids and glycolipids from the Mtb cell wall are thought to be virulence factors that mediate host-pathogen interactions. An intriguing example is Sulfolipid-1 (SL-1), a sulfated glycolipid that has been implicated in Mtb pathogenesis, although no direct role for SL-1 in virulence has been established. Previously, we described the biochemical activity of the sulfotransferase Stf0 that initiates SL-1 biosynthesis. Here we show that a stf0-deletion mutant exhibits augmented survival in human but not murine macrophages, suggesting that SL-1 negatively regulates the intracellular growth of Mtb in a species-specific manner. Furthermore, we demonstrate that SL-1 plays a role in mediating the susceptibility of Mtb to a human cationic antimicrobial peptide in vitro, despite being dispensable for maintaining overall cell envelope integrity. Thus, we hypothesize that the species-specific phenotype of the stf0 mutant is reflective of differences in antimycobacterial effector mechanisms of macrophages. 相似文献
65.
66.
Madhulika Singh Uma Jaiswal V. S. Jaiswal 《Journal of plant biochemistry and biotechnology.》2001,10(2):133-137
Thidiazuron (TDZ) stimulated shoot proliferation from different seedling explants (i.e., shoot, basal node, node and apical segment) of bamboo (Dendrocalamus strictus) when incorporated in half-strength Murashige and Skoog (MS) medium having 2% (w/v) sucrose. All the concentrations of TDZ (0.01 to 1.0 mg l?1) tried were effective in shoot proliferation. Maximum shoots (14.8 ± 1.0) were obtained from the shoot explants cultured in 0.5 mg l?1 TDZ supplemented halfstrength MS liquid medium for 21 days and subsequently transferred to the same medium devoid of TDZ. The longer culture period (i.e. 28 and 35 days) in TDZ medium caused reduction in shoot proliferation. The shoots regenerated with lower concentrations of TDZ treatment (i.e. 0.01 to 0.1 mg l?1) rooted in half-strength MS liquid medium. The shoots formed with 0.5 mg l?1 TDZ treatment did not root in basal medium and required auxin supplementation in the medium for rooting and about 55% shoots produced roots in 1.0 mg l?1 IBA supplemented medium. The shoots formed with 1.0 mg l?1 TDZ did not root even after auxin treatment. The well rooted shoots transplanted to plastic pots filled with sand and garden soil (1:1) mixture showed 98% establishment. 相似文献
67.
Madhulika?Singh Uma?Jaiswal Vijai?Shanker?JaiswalEmail author 《In vitro cellular & developmental biology. Plant》2003,39(2):229-233
Summary Sodium chloride-tolerant plantlets of Dendrocalamus strictus were regenerated successfully from NaCl-tolerant embryogenic callus via somatic embryogenesis. The selection of embryogenic
callus tolerant to 100 mM NaCl was made by exposing the callus to increasing (0–200 mM) concentrations of NaCl in Murashige and Skoog medium having 3% (w/v) sucrose, 0.8% (w/v) agar, 3.0 mg l−1 (13.6 μM) 2,4-dichlorophenoxyacetic acid (2,4-D), and 0.5mg l−1 (2.3μM) kinetin (callus initiation medium). The tolerance of the selected embryogenic callus to 100 mM NaCl was stable through three successive transfers on NaCl-free callus initiation medium. The tolerant embryogenic callus
had high levels of Na+, sugar, free amino acids, and proline but a slight decline was recorded in K+ level. The stable 100 mM NaCl-tolerant embryogenic callus differentiated somatic embryos on maintenance medium [MS medium +3% sucrose +0.8% agar +2.0
mg l−1 (9.0 μM) 2,4-D+0.5 mg l−1 (2.3 μM) kinetin] supplemented with different (0–200 mM) concentrations of NaCl. About 39% of mature somatic embryos tolerant to 100 mM NaCl germinated and converted into plantlets in germination medium [half-strength MS+2% sucrose+0.02 mg l−1 (0.1 μM) α-naphthaleneacetic acid +0.1 mg l−1 (0.49 μM) indole-3-butyric acid] containing 100 mM NaCl. Of these plantlets about 31% established well on transplantation into a garden soil and sand (1:1) mixture containing
0.2% (w/w) NaCl. 相似文献
68.
Conserved motifs in somatostatin,D2-dopamine,and alpha 2B-adrenergic receptors for inhibiting the Na-H exchanger,NHE1 总被引:3,自引:0,他引:3
Lin CY Varma MG Joubel A Madabushi S Lichtarge O Barber DL 《The Journal of biological chemistry》2003,278(17):15128-15135
Receptor subtypes within families of G protein-coupled receptors that are activated by similar ligands can regulate distinct intracellular effectors. We identified conserved motifs within intracellular domains 2 and 3 of selective subtypes of several G protein-coupled receptor families that confer coupling to the Na-H exchanger, NHE1. A T(s,p)V motif within intracellular domain 2 and a QQ(r) motif within intracellular domain 3 are shared by the somatostatin receptor subtypes SSTR1, -3, and -4, which couple to the inhibition of NHE1, but not by SSTR2 and -5, which do not signal to NHE1. Only the collective substitution of cognate SSTR2 residues with these two motifs conferred the ability of mutant SSTR2 to inhibit NHE1. Both motifs are present in D(2)-dopamine receptors, which inhibit NHE1, and in alpha(2B)-adrenergic receptors, which couple to the inhibition of NHE1, but not in alpha(2A)-adrenergic receptors, which do not regulate NHE1. These findings indicate that motifs shared by different subfamilies of G protein-coupled receptors, but not necessarily by receptor subtypes within a subfamily, can confer coupling to a common effector. 相似文献
69.
70.
Madhulika B. Gupta 《Journal of cell communication and signaling》2015,9(2):111-123
Fetal growth restriction (FGR) increases the risk of perinatal complications and predisposes the infant to developing metabolic, cardiovascular, and neurological diseases in childhood and adulthood. The pathophysiology underlying FGR remains poorly understood and there is no specific treatment available. Biomarkers for early detection are also lacking. The insulin-like growth factor (IGF) system is an important regulator of fetal growth. IGF-I is the primary regulator of fetal growth, and fetal circulating levels of IGF-I are decreased in FGR. IGF-I activity is influenced by a family of IGF binding proteins (IGFBPs), which bind to IGF-I and decrease its bioavailability. During fetal development the predominant IGF-I binding protein in fetal circulation is IGFBP-1, which is primarily secreted by the fetal liver. IGFBP-1 binds IGF-I and thereby inhibits its bioactivity. Fetal circulating levels of IGF-I are decreased and concentrations of IGFBP-1 are increased in FGR. Phosphorylation of human IGFBP-1 at specific sites markedly increases its binding affinity for IGF-I, further limiting IGF-I bioactivity. Recent experimental evidence suggests that IGFBP-1 phosphorylation is markedly increased in the circulation of FGR fetuses suggesting an important role of IGFBP-1 phosphorylation in the regulation of fetal growth. Understanding of the significance of site-specific IGFBP-1 phosphorylation and how it is regulated to contribute to fetal growth will be an important step in designing strategies for preventing, managing, and/or treating FGR. Furthermore, IGFBP-1 hyperphosphorylation at unique sites may serve as a valuable biomarker for FGR. 相似文献