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Query: UNIPROT:P06889 (Mol)
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The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by asbestos in mouse embryo fibroblast PW cells. Exposure of cells to asbestos led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of asbestos-induced H2O2 with N-acety-L-cyteine (NAC, a general antioxidant) or catalase (a specific H2O2 inhibitor) resulted in inhibition of NFAT activation. In contrast, an increase in H2O2 generation by the addition of superoxide dismutase (SOD) slightly enhanced asbestos-induced NFAT activation. In addition, pretreatment of cells with sodium formate did not exhibit any inhibition of NFAT activity induced by asbestos. These results demonstrated that H2O2 appeared to play an important role in asbestos-induced NFAT transactivation. Furthermore, it was observed that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) not only resulted in NFAT activation by itself, but also enhanced asbestos-induced NFAT induction. Pretreatment of cells with cyclosporin A (CSA), a pharmacological inhibitor of the phosphatase calcineurin, blocked both asbestos- and TPA plus asbestos-induced NFAT activation. These data suggest that asbestos is able to induce NFAT activation through H2O2-dependent and CSA-sensitive pathways, which may be involved in asbestos-induced carcinogenesis.
Mol Cell Biochem
PMID:Involvement of hydrogen peroxide in asbestos-induced NFAT activation. 1216 29

The present study investigated the differential requirement of ROS in UV-induced activation of these pathways. Exposure of the mouse epidermal C141 cells to UV radiation led to generation of ROS as measured by electron spin resonance (ESR) and by H2O2 and O2. fluorescence staining assay. Treatment of cells with UV radiation or H2O2 also markedly activated Erks, JNKs, p38 kinase and led to increases in phosphorylation of Akt and p70(S6k) in mouse epidermal JB6 cells. The scavenging of UV-generated H2O2 by N-acety-L-cyteine (NAC, a general antioxidant) or catalase (a specific H2O2 inhibitor) inhibited UV-induced activation of JNKs, p38 kinase, Akt and p70(S6k), while it did not show any inhibitory effects on Erks activation. Further, pretreatment of cells with sodium formate (an .OH radical scavenger) or superoxide dismutase (O2-. radical scavenger) did not inhibit any of these pathways. These results demonstrate that H2O2 generation is required for UV-induced phosphorylation of Akt and p70(S6k), and involved in activation of JNKs and p38 kinase, but not Erks.
Mol Cell Biochem
PMID:Differential role of hydrogen peroxide in UV-induced signal transduction. 1216 63

The petunia NAM and ArabidopsisATAF1 and CUC2 genes define the conserved NAC domain. In petunia, loss-of-function nam mutants result in embryos that fail to elaborate shoot apical meristems (SAM), and nam seedlings do not develop shoots and leaves. We have isolated a NAC domain gene, AtNAM, from an Arabidopsis developing seed cDNA library. Expression of AtNAM mRNA is restricted primarily to the region of the embryo including the SAM. The AtNAM gene contains three exons and is located on Chromosome 1. In vivo assays in yeast demonstrate that AtNAM encodes a transcription factor and that the NAC domain includes a specific DNA binding domain (DBD). The AtNAM DBD is contained within a 60 amino acid region which potentially folds into a helix-turn-helix motif that specifically binds to the CaMV 35S promoter. The putative transcriptional activation domain is located in the C-terminal region of the protein, a highly divergent region among NAC domain-containing genes. The Arabidopsis genome contains 90 predicted NAC domain genes; we refer to these collectively as the AtNAC superfamily. The first two exons of all members of this superfamily encode the NAC domain. Most AtNAC genes contain three exons with the last exon encoding an activation domain. A subfamily of AtNAC genes contains additional terminal exons coding for protein domains whose functions are unknown.
Plant Mol Biol 2002 Sep
PMID:Molecular characterization of AtNAM: a member of the Arabidopsis NAC domain superfamily. 1217 16

Cardiac hypertrophy is an adaptive response to increases in blood pressure. Recent studies indicate that the hypertrophic process is associated with increases in intracellular oxidative stress in cardiomyocytes. We hypothesize that superoxide anion mediates the hypertrophic response and that antioxidant therapy may be effective in attenuating cardiac hypertrophy. Neonatal rat cardiac myocytes were stimulated with angiotensin II (AngII, 1 microM) with and without various antioxidants. N-acetylcysteine (NAC, 10 mM) and probucol (50 microM), and to a lesser extent, vitamin C (500 microM) and reduced glutathione (1 mM), inhibited AngII-induced [(3)H]-leucine uptake and atrial natriuretic factor (ANF) promoter activity. The hypertrophic response is mediated by superoxide anion (O(2)(-).) since cell-permeable polyethylene glycol (PEG)-conjugated superoxide dismutase (50 U/ml), but not PEG-catalase (500 U/ml), attenuated AngII-induced [(3)H]-leucine uptake and ANF promoter activity. Furthermore, NAC blocked AngII-induced increase in myocardial oxidative stress, decreased the expression of ANF and myosin light chain-2v, and inhibited the re-organization of cytoskeletal proteins, desmin and alpha-actinin. These effects of AngII were abolished by angiotensin type 1 receptor blocker, losartan, but not type 2 receptor blocker, PD123319. Indeed, co-administration of losartan (10 mg/kg/d, 14 d) or NAC (200 mg/kg/d, 14 d) inhibited AngII-induced O(2)(-). production and cardiac hypertrophy in rats without affecting blood pressure. These findings indicate that the generation of O(2)(-). contributes to oxidant-induced hypertrophic response and suggest that antioxidant therapy may have beneficial effects in cardiac hypertrophy.
J Mol Cell Cardiol 2003 Jul
PMID:NADPH oxidase-derived superoxide anion mediates angiotensin II-induced cardiac hypertrophy. 1281 76

The majority of cytosolic proteins in eukaryotes contain a covalently linked acetyl moiety at their very N terminus. The mechanism by which the acetyl moiety is efficiently transferred to a large variety of nascent polypeptides is currently only poorly understood. Yeast N(alpha)-acetyltransferase NatA, consisting of the known subunits Nat1p and the catalytically active Ard1p, recognizes a wide range of sequences and is thought to act cotranslationally. We found that NatA was quantitatively bound to ribosomes via Nat1p and contained a previously unrecognized third subunit, the N(alpha)-acetyltransferase homologue Nat5p. Nat1p not only anchored Ard1p and Nat5p to the ribosome but also was in close proximity to nascent polypeptides, independent of whether they were substrates for N(alpha)-acetylation or not. Besides Nat1p, NAC (nascent polypeptide-associated complex) and the Hsp70 homologue Ssb1/2p interact with a variety of nascent polypeptides on the yeast ribosome. A direct comparison revealed that Nat1p required longer nascent polypeptides for interaction than NAC and Ssb1/2p. Delta nat1 or Delta ard1 deletion strains were temperature sensitive and showed derepression of silent mating type loci while Delta nat5 did not display any obvious phenotype. Temperature sensitivity and derepression of silent mating type loci caused by Delta nat1 or Delta ard1 were partially suppressed by overexpression of SSB1. The combination of data suggests that Nat1p presents the N termini of nascent polypeptides for acetylation and might serve additional roles during protein synthesis.
Mol Cell Biol 2003 Oct
PMID:The yeast N(alpha)-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides. 1451 7

Subtractive expressed sequence tag analysis and screening of cDNA libraries derived from Brassica napus leaves subjected to mechanical wounding, flea beetle feeding or cold temperatures revealed eight genes encoding NAC-domain transcription factors. The genes were found to be differentially regulated in response to biotic and abiotic stresses including wounding, insect feeding, Sclerotinia sclerotiorum infection, cold shock and dehydration. Five BnNAC proteins were orthologous to Arabidopsis thaliana ATAF1 or ATAF2 and gave rise to developmental abnormalities similar to the A. thaliana nam and cuc mutants when expressed ectopically in A. thaliana. Transgenic lines expressing BnNAC14, exhibited large leaves, thickened stems and hyper-developed lateral root systems similar to that observed with A. thaliana NAC1, but also were delayed in bolting and lacked an apical dominant tap root. Several of the BnNAC proteins were capable of activating gene expression in yeast and recognized an element within the CaMV35S promoter. A yeast two-hybrid screen revealed that BnNAC14 interacted with other select BnNAC proteins in vitro and identified an additional BnNAC gene, BnNAC485. The protein interaction and transcriptional activation domains were mapped by deletion analysis.
Plant Mol Biol 2003 Oct
PMID:Molecular characterization of Brassica napus NAC domain transcriptional activators induced in response to biotic and abiotic stress. 1475 May 26

Members of the plant-specific gene family referred to as the NAC family (for NAM-ATAF-CUC-related) are involved in various functions including the regulation of plant development. However, no detailed molecular characterization of any member of the NAC family has yet been reported from monocots. Here, we report such a characterization of ONAC300, a novel NAC-family gene identified using a cDNA cloned from microdissected phloem cells of rice. The predicted ONAC300 protein sequence falls into the NAM subgroup, which also contains the proteins CUC1 and CUC2 from Arabidopsis, CUP from snapdragon, CmNACP from pumpkin and NAM from petunia. High levels of ONAC300 mRNA were detected by in situ hybridization in developing shoot apical meristem (SAM) and in the associated young leaves. The use of an ONAC300:: GUS reporter gene revealed that the ONAC300 promoter was expressed predominantly in developing vascular tissues of the leaves and roots. The construct was also expressed in anther filaments, rachis and carpel styles. RT-PCR analysis further revealed that the levels of ONAC300 transcripts were higher in leaves, roots and culms than in panicles. The observed expression pattern of ONAC300 is quite different from those of the dicot NAC genes previously reported. Thus, ONAC300 is a novel member of the NAC family which is expressed at very early developmental stages in the shoot, root and flower, as well as in the mature phloem of vascular tissues in rice.
Mol Genet Genomics 2005 Feb
PMID:Molecular characterization of ONAC300, a novel NAC gene specifically expressed at early stages in various developing tissues of rice. 1565 22

Heat shock proteins (HSPs) are a family of highly conserved proteins that are induced by a number of stresses including toxic metals. Heat shock proteins expression has been reported to be an early and sensitive biomarker of cell stress. Arsenic is a naturally occurring metal that exists widely in the environment and is used in several industries. Exposure to arsenic is associated with the development of pulmonary cancers. We monitored changes in Hsp70 and markers of oxidative injury induced by arsenic in human pulmonary epithelial cells (BEAS-2B). Hsp70 protein, mRNA and reactive oxygen species (ROS) generation were measured after exposing cells to arsenic as markers of injury. Hsp70 protein expression showed significant 7.9-fold and 31.5-fold increase using Western blotting and ELISA assay, respectively, at a 50 microM As(III) with a 12 h exposure and an 12 h recovery time. Hsp70A and Hsp70B mRNA expression showed a two-fold increase and Hsp70C mRNA expression showed a six-fold increase. As(III)-induced Hsp70 protein expression was inhibited significantly by catalase and NAC, indicating mediation of ROS in Hsp70 expression. Intracellular glutathione (GSH) was significantly depleted by As(III) exposure. Lipid peroxidation by-product, 8-isoprostane, was increased six-fold at 24 h exposure to 20 microM As(III). Electron spin resonance and confocal microscope studies also showed As(III)-stimulated ROS generation. These results suggest that cellular injury by arsenic is mediated through ROS generation resulting in the expression of Hsp70. It is possible that Hsp70 may prove to be a sensitive biomarker for arsenic exposure with other markers of oxidative stress in human serum.
Mol Cell Biochem 2005 Sep
PMID:Heat shock protein 70 as an indicator of early lung injury caused by exposure to arsenic. 1613 27

All aerial parts of a higher plant originate from the shoot apical meristem (SAM), which is initiated during embryogenesis as a part of the basic body plan. In contrast to dicot species, the SAM in Zea mays is not established at an apico-central, but at a lateral position of the transition stage embryo. Genetic and molecular studies in dicots have revealed that members of the NAC gene family of plant-specific transcription factors such as NO APICAL MERISTEM (NAM) from Petunia or the CUP-SHAPED COTYLEDON (CUC) genes from Arabidopsis contribute essential functions to the establishment of the SAM and cotyledon separation. As an approach to the understanding of meristem formation in a monocot species, members of the maize NAC family highly related to the NAM/CUC genes were isolated and characterized. Our phylogenetic analysis indicates that two distinct NAM and CUC3 precursors already existed prior to the separation of mono- and dicot species. The allocation of the two maize paralogues, ZmNAM1 and ZmNAM2 together with PhNAM, AtCUC2 and AmCUP in one sub-branch and the corresponding expression patterns support their contribution to SAM establishment. In contrast, the ZmCUC3 orthologue is associated with boundary specification at the SAM periphery, where it visualizes which fraction of cells in the SAM is committed to a new leaf primordium. Other maize NAC gene family members are clearly positioned outside of this NAM/CUC3 branch and also exhibit highly cell type-specific expression patterns.
Plant Mol Biol 2005 Jul
PMID:Pattern formation in the monocot embryo as revealed by NAM and CUC3 orthologues from Zea mays L. 1615 42

Sodium salicylate, one of anti-inflammatory agents, is known to partially induce the heat shock response: it stimulates the DNA-binding of heat shock factor 1 (HSF1) without inducing heat shock gene expression. Here we show that when C6 glioma cells are recovered from sodium salicylate treatment, they highly induce heat shock protein 72 (HSP72), but not HSP73 and HSP90, demonstrating that salicylate-induced inert HSF1 can be fully activated into a transcriptionally competent form by sodium salicylate recovery (SR)-specific mechanism. Fluorescent analysis using 2',7'-dichlorodihydrofluorescein diacetate revealed that sodium salicylate enhanced reactive oxygen species (ROS) production. N-acetyl-L-cysteine (NAC, a ROS scavenger) completely suppressed SR-induced HSP72 synthesis and HSP72 promoter-driven CAT reporter gene transcription as well as salicylate-induced HSF1-DNA binding, indicating a critical role(s) of ROS in the SR-induced HSP72 gene regulation. We also show that treatment of C6 cells with sodium salicylate activated p38MAPK and inactivated ERK1/2 in a ROS-independent manner and activities of these protein kinases returned during recovery period to the control level. Inhibiting p38MAPK and ERK1/2 with the p38MAPK inhibitors (SB203580 and SB202190) and the MEK1/2 inhibitor (PD98059 and U0126) or with expression of dominant negative p38MAPK and ERK1/2 abolished SR-induced HSP72 synthesis and HSP70 promoter-driven CAT activity. However, sodium salicylate-induced HSF1-DNA binding was not affected by the p38MAPK inhibitor or the MEK1/2 inhibitor. These findings suggest that sodium salicylate partially activates HSF1 via ROS production and p38MAPK activation and the salicylate-induced inert HSF1 can be fully activated into a transcriptionally competent form by the ERK1/2 signaling pathways that are activated independently of ROS during SR.
Int J Mol Med 2005 Nov
PMID:Implication of reactive oxygen species, ERK1/2, and p38MAPK in sodium salicylate-induced heat shock protein 72 expression in C6 glioma cells. 1621 Dec 53


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