Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A central dogma in biology is the conversion of genetic information into active proteins. The biosynthesis of proteins by ribosomes and the subsequent folding of newly made proteins represent the last crucial steps in this process. To guarantee the correct folding of newly made proteins, a complex chaperone network is required in all cells. In concert with ongoing protein biosynthesis, ribosome-associated factors can interact directly with emerging nascent polypeptides to protect them from degradation or aggregation, to promote folding into their native structure, or to otherwise contribute to their folding program. Eukaryotic cells possess two major ribosome-associated systems, an Hsp70/Hsp40-based chaperone system and the functionally enigmatic NAC complex, whereas prokaryotes employ the Trigger Factor chaperone. Recent structural insights into Trigger Factor reveal an intricate cradle-like structure that, together with the exit site of the ribosome, forms a protected environment for the folding of newly synthesized proteins.
Cell Mol Life Sci 2005 Dec
PMID:Molecular guardians for newborn proteins: ribosome-associated chaperones and their role in protein folding. 1623 Oct 86

Yeast, Saccharomyces cerevisiae, exposed to CdCl2 for 17 h was analysed with reference to survival, MTs and oxidative stress biomarkers. An enhanced accumulation of MDA and the increased activities of SOD and GPx in the Cd-treated yeasts under aerobic condition indicated CdCl2-caused oxidative stress in S. cerevisiae. MTs were significantly induced by CdCl2 under aerobic condition and the induced MTs contents were positively correlated with the accumulation of MDA in this study. However, MTs induction can be prominently inhibited by coincubation with NAC or anaerobic culture via eliminating ROS. This oxidative stress reduction was reflected by the decreases in MDA level and SOD and GPx activities. The results suggest that MTs inductive activity of cadmium in yeast cells was mediated by oxidative stress. In addition, increase of MTs contents was observed in cells untreated with CdCl2 under anaerobic conditions or coincubation with NAC, suggesting MTs are also susceptive to reductive stress.
Mol Cell Biochem 2005 Dec
PMID:Cadmium induced MTs synthesis via oxidative stress in yeast Saccharomyces cerevisiae. 1631 15

Activated matrix metalloproteinases (MMPs) in patients with acute coronary syndromes may contribute to plaque destabilization. Tumor necrosis factor-alpha (TNF-alpha) enhances NAD (P) H oxidase-dependent reactive oxygen species (ROS) formation and ROS induce MMP-2. In the present study, the effects of a potent water-soluble antioxidant, salvianolic acid B (SalB), derived from a Chinese herb, Salvia miltiorrhiza, on the expression of MMP-2 by TNF-alpha-treated human aortic smooth muscle cells (HASMCs) were investigated. In this study, salvianolic acid B scavenged H2O2 in a dose-dependent manner in test tube. We found that SalB, as well as NADPH oxidase inhibitors, DPI or apocynin, and antioxidant NAC, inhibited TNF-alpha-induced MMP-2 mRNA, protein expression, and gelatinolytic activity in HASMCs in a concentration-dependent manner. We also observed a dose-dependent decrease in ROS production and NADPH oxidase activity induced by TNF-alpha in the presence of SalB. SalB also significantly inhibited angiotensin II or H2O2-induced MMP-2 mRNA and protein expression and gelatinolytic activity in HASMCs. Our data point out that the importance of NADPH oxidase-dependent ROS generation in the control of SalB inhibition of TNF-alpha-induced MMP-2 expression and activity.
J Mol Cell Cardiol 2006 Jul
PMID:Salvianolic acid B from Salvia miltiorrhiza inhibits tumor necrosis factor-alpha (TNF-alpha)-induced MMP-2 upregulation in human aortic smooth muscle cells via suppression of NAD(P)H oxidase-derived reactive oxygen species. 1671 3

Cytoplasmic sulfate for sulfation reactions may be derived either from extracellular fluids or from catabolism of sulfur-containing amino acids and other thiols. In vitro studies have pointed out the potential relevance of sulfur-containing amino acids as sources for sulfation when extracellular sulfate concentration is low or when its transport is impaired such as in DTDST [DTD (diastrophic dysplasia) sulfate transporter] chondrodysplasias. In the present study, we have considered the contribution of cysteine and cysteine derivatives to in vivo macromolecular sulfation of cartilage by using the mouse model of DTD we have recently generated [Forlino, Piazza, Tiveron, Della Torre, Tatangelo, Bonafe, Gualeni, Romano, Pecora, Superti-Furga et al. (2005) Hum. Mol. Genet. 14, 859-871]. By intraperitoneal injection of [35S]cysteine in wild-type and mutant mice and determination of the specific activity of the chondroitin 4-sulfated disaccharide in cartilage, we demonstrated that the pathway by which sulfate is recruited from the intracellular oxidation of thiols is active in vivo. To check whether cysteine derivatives play a role, sulfation of cartilage proteoglycans was measured after treatment for 1 week of newborn mutant and wild-type mice with hypodermic NAC (N-acetyl-L-cysteine). The relative amount of sulfated disaccharides increased in mutant mice treated with NAC compared with the placebo group, indicating an increase in proteoglycan sulfation due to NAC catabolism, although pharmacokinetic studies demonstrated that the drug was rapidly removed from the bloodstream. In conclusion, cysteine contribution to cartilage proteoglycan sulfation in vivo is minimal under physiological conditions even if extracellular sulfate availability is low; however, the contribution of thiols to sulfation becomes significant by increasing their plasma concentration.
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PMID:In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation. 1671 39

Endothelial dysfunction is one of the earliest pathological effects of cigarette smoking. Vascular endothelial growth factor (VEGF) has been shown to be an important regulator of endothelial healing and growth. Accordingly, we tested the hypothesis that cigarette smoke exposure impairs VEGF actions in endothelial cells. In human umbilical vein endothelial cells (HUVECs), cigarette smoke extracts (CSE) inhibited VEGF-induced tube formation in the matrigel assay. CSE did not affect HUVECs proliferation, but significantly reduced cellular migration in response to VEGF. This impaired migratory activity was associated with a reduced expression of alpha(v)beta(3), alpha(v)beta(5), alpha(5)beta(1) and alpha(2)beta(1) integrins. The Akt/eNOS/NO pathway has been shown to be important for VEGF-induced endothelial cell migration. We found that CSE inhibited Akt/eNOS phosphorylation and NO release in VEGF-stimulated HUVECs. This was associated with an increased generation of reactive oxygen species (ROS). Importantly, in HUVECs exposed to CSE, treatment with antioxidants (NAC, vitamin C) reduced ROS formation and rescued VEGF-induced NO release, cellular migration and tube formation. Moreover, treatment with NO donors (SNAP, SNP) or a cGMP analog (8-Br-cGMP) rescued integrin expression, cellular migration and tube formation in endothelial cells exposed to CSE. (1) Cigarette smoke exposure impairs VEGF-induced endothelial cell migration and tube formation. (2) The mechanism involves increased generation of ROS, decreased expression of surface integrins together with a blockade of the Akt/eNOS/NO pathway. (3) These findings could contribute to explain the negative effect of cigarette smoking on endothelial function and vessel growth.
J Mol Cell Cardiol 2006 Aug
PMID:Cigarette smoke exposure impairs VEGF-induced endothelial cell migration: role of NO and reactive oxygen species. 1680 64

Arabidopsis thaliana BRAHMA (BRM, also called AtBRM) is a SNF2 family protein homolog of Brahma, the ATPase of the Drosophila SWI/SNF complex involved in chromatin remodeling during transcription. Here we show that, in contrast to its Drosophila counterpart, BRM is not an essential gene. Thus, homozygous BRM loss of function mutants are viable but exhibit numerous defects including dwarfism, altered leaf and root development and several reproduction defects. The analysis of the progeny of self-fertilized heterozygous brm plants and reciprocal crosses between heterozygous and wild type plants indicated that disruption of BRM reduced both male and female gametophyte transmission. This was consistent with the presence of aborted ovules in the self-fertilized heterozygous flowers that contained arrested embryos predominantly at the two terminal cells stage. Furthermore, brm homozygous mutants were completely sterile. Flowers of brm loss-of-function mutants have several developmental abnormalities, including homeotic transformations in the second and third floral whorls. In accordance with these results, brm mutants present reduced levels of APETALA2, APETALA3, PISTILLATA and NAC-LIKE, ACTIVATED BY AP3/PI. We have previously shown that BRM strongly interacts with AtSWI3C. Now we extend our interaction studies demonstrating that BRM interacts weakly with AtSWI3B but not with AtSWI3A or AtSWI3D. In agreement with these results, the phenotype described in this study for brm plants is very similar to that previously described for the AtSWI3C mutant plants, suggesting that both proteins participate in the same genetic pathway or form a molecular complex.
Plant Mol Biol 2006 Sep
PMID:The putative SWI/SNF complex subunit BRAHMA activates flower homeotic genes in Arabidopsis thaliana. 1684 77

M-CSF induces PI 3-kinase activation, resulting in reactive oxygen species (ROS) production. Previously, we reported that ROS mediate macrophage colony-stimulating factor (M-CSF)-induced extracellular regulated kinase (Erk) activation and monocyte survival. In this work, we hypothesized that M-CSF-stimulated ROS products modulated Akt1 and p38 activation. Furthermore, we sought to clarify the source of these ROS and the role of ROS and Akt in monocyte/macrophage survival. Macrophages from p47(phox-/-) mice, lacking a key component of the NADPH oxidase complex required for ROS generation, had reduced cell survival and Akt1 and p38 mitogen-activated protein kinase (MAPK) phosphorylation compared with wild-type macrophages in response to M-CSF stimulation, but had no difference in M-CSF-stimulated Erk. To understand how ROS affected monocyte survival and signaling, we observed that NAC and DPI decreased cell survival and Akt1 and p38 MAPK phosphorylation. Using bone marrow-derived macrophages from mice expressing constitutively activated Akt1 (Myr-Akt1) or transfecting Myr-Akt1 constructs into human peripheral monocytes, we concluded that Akt is a positive regulator of monocyte survival. Moreover, the p38 MAPK inhibitor, SB203580, inhibited p38 activity and M-CSF-induced monocyte survival. These findings demonstrate that ROS generated from the NADPH oxidase complex contribute to monocyte/macrophage survival induced by M-CSF via regulation of Akt and p38 MAPK.
Am J Respir Cell Mol Biol 2007 Jan
PMID:The role of the NADPH oxidase complex, p38 MAPK, and Akt in regulating human monocyte/macrophage survival. 1693 6

Anionic surfactant micelle-mediated extraction with sodium dodecylsulfate (SDS) was applied as preconcentration step prior to fluorescence spectrophotometer without further cleanup step. The obtained surfactant-rich phase was diluted to a fixed volume with water-miscible solvents. Carbaryl and its metabolite 1-naphthol were used as test compounds. The detection limits (LODs) of the method were in the microgram per liter area. Recoveries obtained from four real water samples ranged from 90.7 to 98.6%. Under the optimum experimental conditions, the method described showed a good precision, with relative standard deviations (R.S.D.) of less than 6%. According to the results, this approach reduced the viscidity of the surfactant-rich phase and made the combination of fluorescence spectrophotometer with anionic surfactant micelle-mediated extraction much easier.
Spectrochim Acta A Mol Biomol Spectrosc 2007 Jun
PMID:Determination of carbaryl and its metabolite 1-naphthol in water samples by fluorescence spectrophotometer after anionic surfactant micelle-mediated extraction with sodium dodecylsulfate. 1696 74

NAC proteins are plant-specific transcriptional regulators. ATAF1 was one of the first identified NAC proteins in Arabidopsis. In present study, we characterized the ATAF1 expression and biological function in response to water deficit stress. ATAF1 mRNA expression was strongly induced by dehydration and abscisic acid (ABA) treatment, but inhibited by water treatment, suggesting a general role in drought stress responses. Transient expression analysis in onion epidermal cells indicated the nuclear localization for the ATAF1::GFP fusion protein. Yeast transactivation analysis showed that ATAF1 had ability to activate reporter gene expression. Furthermore, domain deletion analysis revealed that the ATAF1 transactivation activity was conferred by its C-terminal domain. When ATAF1 gene was knocked out by T-DNA insertions, Arabidopsis ataf1-1 and ataf1-2 mutants displayed a recovery rate about seven times higher than wild-type plants in drought response test. This ataf1 phenotype was coincident with the enhanced expression of stress responsive marker genes, such as COR47, ERD10, KIN1, RD22 and RD29A under drought stress. Above evidences suggest that ATAF1, as a transcriptional regulator, negatively regulates the expression of stress responsive genes under drought stress in Arabidopsis.
Plant Mol Biol 2007 Jan
PMID:A novel drought-inducible gene, ATAF1, encodes a NAC family protein that negatively regulates the expression of stress-responsive genes in Arabidopsis. 1703 11

Cellular cytoskeletal remodeling reflects alterations in local biochemical and mechanical changes in terms of stress that manifests relocation of signaling molecules within and across the cell. Although stretching due to load and chemical changes by high homocysteine (HHcy) causes cytoskeletal re-arrangement, the synergism between stretch and HHcy is unclear. We investigated the contribution of HHcy in cyclic stretch-induced focal adhesion (FA) protein redistribution leading to cytoskeletal re-arrangement in mouse aortic endothelial cells (MAEC). MAEC were subjected to cyclic stretch (CS) and HHcy alone or in combination. The redistribution of FA protein, and small GTPases were determined by Confocal microscopy and Western blot techniques in membrane and cytosolic compartments. We found that each treatment induces focal adhesion kinase (FAK) phosphorylation and cytoskeletal actin polymerization. In addition, CS activates and membrane translocates small GTPases RhoA with minimal effect on Rac1, whereas HHcy alone is ineffective in both GTPases translocation. However, the combined effect of CS and HHcy activates and membrane translocates both GTPases. Free radical scavenger NAC (N-Acetyl-Cysteine) inhibits CS and HHcy-mediated FAK phosphorylation and actin stress fiber formation. Interestingly, CS also activates and membrane translocates another FA protein, paxillin in HHcy condition. Cytochalasin D, an actin polymerization blocker and PI3-kinase inhibitor Wortmannin inhibited FAK phosphorylation and membrane translocation of paxillin suggesting the involvement of PI3K pathway. Together our results suggest that CS- and HHcy-induced oxidative stress synergistically contribute to small GTPase membrane translocation and focal adhesion protein redistribution leading to endothelial remodeling.
Mol Cell Biochem 2007 Aug
PMID:Homocysteine-induced biochemical stress predisposes to cytoskeletal remodeling in stretched endothelial cells. 1752 26


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