Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ligusticum chuanxiong and Angelica sinensis have been widely used in traditional Chinese medicine to treat some pathological settings such as atherosclerosis and hypertension. We determined the protective effect of the extract of Ligusticum chuanxiong and Angelica sinensis (ELCAS) on human umbilical vein endothelial cells (ECV304) damage induced by hydrogen peroxide. ECV304 cells were pre-treated with ELCAS and exposed to 5 mM hydrogen peroxide. The results show that ELCAS dose- and time-dependently protected ECV304 cells against hydrogen peroxide damage and suppressed the production of reactive oxygen species (ROS). The decrement of ROS may be associated with increased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Western blot analysis revealed that ELCAS significantly increased the phosphorylation of ERK and promoted eNOS expression. These observations indicate that ELCAS protected ECV304 cells against hydrogen peroxide damage by enhancing the antioxidative ability, activating ERK and eNOS signaling pathway. Our data also provide new evidence of Ligusticum chuanxiong and Angelica sinensis in preventing both cardiovascular and cerebrovascular diseases.
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PMID:Protective effect of Ligusticum chuanxiong and Angelica sinensis on endothelial cell damage induced by hydrogen peroxide. 1526 76

The ETV6-NTRK3 gene fusion, first identified in the chromosomal translocation in congenital fibrosarcoma, encodes a chimeric protein tyrosine kinase with potent transforming activity. ETV6-NTRK3-dependent transformation involves the joint action of NTRK3 signaling pathways, and aberrant cell cycle progression resulting from activation of Mek1 and Akt. The level of glutathione (GSH) was found to be markedly increased in ETV6-NTRK3-transformed NIH3T3 cells. The activities of the two GSH biosynthetic enzymes as well as of glutathione peroxidase, together with their mRNAs, were also higher in the transformed cells. The transformed cells were able to grow in the presence of GSH-depleting agents, whereas the control cells were not. L-Buthionine-(S,R)-sulfoximine (BSO) inhibited activation of Mek1 and Akt in the transformed NIH3T3 cells. These observations imply that up-regulation of GSH biosynthesis plays a central role in ETV6-NTRK3-induced transformation.
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PMID:Up-regulation of glutathione biosynthesis in NIH3T3 cells transformed with the ETV6-NTRK3 gene fusion. 1575 Mar 50

RTP801 is a newly discovered stress-response gene that is induced by hypoxia and other cell stress signals. Arsenic is a heavy metal that is linked to carcinogenesis in humans. Here, we investigated the mechanism by which arsenic induces RTP801 transcription. In HaCaT human keratinocytes, arsenite was able to induce a rapid rise in the RTP801 mRNA level. Correspondingly, arsenite treatment was capable of stimulating a 2.5 kb human RTP801 promoter. Such a stimulatory effect was inhibited by co-expression of superoxide dismutase or glutathione peroxidase, and was abrogated by N-acetylcysteine, implying that ROS (reactive oxygen species) were involved in transcriptional regulation of the RTP801 gene. A series of deletion studies with the promoter revealed a critical arsenic-responsive region between -1057 and -981 bp of the promoter. Point mutations of the putative Elk-1 site and the C/EBP (CCAAT/enhancer-binding protein) site within this region were able to reduce the stimulatory effect of arsenite, indicating that Elk-1 and C/EBP are involved in transcriptional regulation of the RTP801 gene by arsenite. Furthermore, a gel mobility-shift assay demonstrated that arsenite was able to mount the rapid formation of a protein complex that bound the arsenic-responsive region as well as the C/EBP-containing sequence. The arsenite stimulation on RTP801 transcription was partly mediated by the ERK (extracellular-signal-regulated kinase) pathway, since the effect of RTP801 was inhibited by a selective ERK inhibitor. In addition, overexpression of Elk-1 and C/EBPbeta was able to elevate the promoter activity. Therefore these studies indicate that RTP801 is a transcriptional target of arsenic in human keratinocytes, and that arsenic and ROS production are linked to Elk-1 and C/EBP in the transcriptional control.
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PMID:Arsenite induces a cell stress-response gene, RTP801, through reactive oxygen species and transcription factors Elk-1 and CCAAT/enhancer-binding protein. 1600 23

In the present study, triphlorethol-A, a phlorotannin, was isolated from Ecklonia cava and its antioxidant properties were investigated. Triphlorethol-A was found to scavenge intracellular reactive oxygen species (ROS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and thus prevented lipid peroxidation. The radical scavenging activity of triphlorethol-A protected the Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen peroxide (H2O2) against cell death, via the activation of ERK protein. Furthermore, triphlorethol-A reduced the apoptotic cells formation induced by H2O2. Triphlorethol-A increased the activities of cellular antioxidant enzymes like, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Hence, from the present study, it is suggestive that triphlorethol-A protects V79-4 cells against H2O2 damage by enhancing the cellular antioxidative activity.
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PMID:Triphlorethol-A from Ecklonia cava protects V79-4 lung fibroblast against hydrogen peroxide induced cell damage. 1603 69

We have previously characterized the cytotoxic action of diallyl disulfide (DADS) on neuroblastoma cells, and we have shown the crucial role of an early and massive reactive oxygen species production in the induction of c-Jun NH(2)-terminal kinase-mediated apoptotic pathway. In the present work, we report that DADS is ineffective in inducing apoptosis in a human adenocarcinoma gastric cell line (AGS). In particular, we show that AGS cells are able to recover from the p53/p21-mediated cell cycle arrest in the G(2)-M phase upon DADS treatment without committing cells to death. This event is most likely due to a peculiar surviving pathway of these cells involving: (a) the formation of mixed disulfides between reduced glutathione (GSH) and protein thiols, (b) a higher and inducible glutathione peroxidase activity, and/or (c) an efficient modulation of the phospho-active levels of the extracellular signal-regulated kinases 1 and 2 (ERK 1/2). Moreover, by increasing glutathione peroxidase expression or GSH concentrations, cell cycle arrest is fully abolished; the apoptotic death is induced by either decreasing the availability of intracellular GSH or inhibiting the reactivation of ERK 1/2. Altogether, our data show that ERK 1/2 participates in the active proliferation of AGS cells and that an efficient reactive oxygen species buffering system makes these cells resistant to DADS-mediated detrimental effects.
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PMID:Glutathione-related systems and modulation of extracellular signal-regulated kinases are involved in the resistance of AGS adenocarcinoma gastric cells to diallyl disulfide-induced apoptosis. 1635 86

Type 2 deiodinase (D2) and type 3 deiodinase (D3) locally achieve the determination of the concentration of T3, which binds to the thyroid hormone receptor with high affinity. D2 converts T4 into T3, and D3 degrades T4 and T3. Neurons take up T3 released by astrocytes, the main cerebral site for the D2 expression. Because oxidative stress is believed to be involved in several neurological disorders, we explored the effects of oxidative stress on D3 and D2 in primary culture of rat astrocytes. H2O2 (250 microm) increased D3 activity with maximal effects around 8 h. Stimulation of D3 activity by H2O2 was synergistic with T4, phorbol ester, and also cAMP. H2O2 (250 microm) did not affect basal D2 activity but inhibited the stimulation of D2 activity by cAMP and factors implicating cAMP-independent pathways in astrocytes, TSH, and phorbol ester. N-Acetyl cysteine and selenium repletion, which respectively increase intracellular glutathione and glutathione peroxidase, inhibited D2 and D3 regulation by H2O2, whereas L-buthionine sulfoximine, which decreases intracellular glutathione, mimicked H2O2 effects. Oxidative stress up-regulated D3 and inhibited cAMP-stimulated D2 by transcriptional mechanisms. A decrease in cAMP by oxidative stress could contribute to the inhibition of cAMP-stimulated D2. Using specific inhibitors of signaling pathways, we show that the ERK pathway was required in D2 and D3 regulation by oxidative stress and that the p38 MAPK pathway was implicated in H2O2-induced D3. We suggest that the expected decrease in T3 might modulate the cellular injury of oxidative stress in some pathological brain conditions.
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PMID:Oxidative stress regulates type 3 deiodinase and type 2 deiodinase in cultured rat astrocytes. 1842 Jul 45

2,3,7,8-Tedtrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic endocrine disruptors and has been reported to induce oxidative stress in the reproductive organs. However, the mechanism by which TCDD induces oxidative stress is unclear. The aim of this study is to examine the role of the general cytokine, TGF-beta1, in TCDD-induced oxidative stress in the male reproductive system. To examine the effect of TCDD on antioxidant enzyme activity, we administered TCDD orally to C57BL/6 mice at 1 microgkg/day for 4 days. Using Smad2-siRNA, we examined the involvement of Smad and non-Smad pathways in TCDD-induced oxidative stress. We also measured the mRNA levels of typical antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and analyzed the activation of TGF-beta1, and the downstream signals, Smad2, Smad4, transcription factors (c-Jun, ATF3), and three major MAPKs (JNK, ERK, p38). After TCDD treatment, the mRNA levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were significantly decreased. In addition, TGF-beta1 activity increased and the receptor-activated protein, Smad2, was activated while Smad4 was not. The levels of major transcription factors, c-Jun and ATF3, and the regulator of these transcription factors, MAPK, were also increased by TCDD administration. The mRNA levels of the 3 antioxidant enzymes in the Smad2-siRNA and TCDD co-treated group were higher than that of the TCDD-only treated group but still decreased when compared to control. C-Jun and ATF3 levels were also increased in Smad2-siRNA and TCDD co-treated testes compared to control. However, the levels of c-Jun and ATF3 were lower than those in the group treated with TCDD only. Of the three MAPKs which showed increase in expression after TCDD treatment, p38 was the only one that showed a decrease with Smad2 inhibition, while both ERK and JNK expression were unaffected. In conclusion, we found that the activated TGF-beta1-Smad pathway is involved in TCDD-induced oxidative stress. Furthermore, the effects of TCDD on the testes are caused by the coordinated action of both Smad and non-Smad pathways.
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PMID:Enhanced TGF-beta1 is involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress in C57BL/6 mouse testis. 1846 41

Prdx6 (peroxiredoxin 6), a bifunctional protein with both GSH peroxidase and PLA(2) (phospholipase A(2)) [aiPLA(2) (acidic calcium-independent PLA(2))] activities, is responsible for the metabolism of lung surfactant phospholipids. We propose that the aiPLA(2) activity of the enzyme is regulated through phosphorylation. Incubation of isolated rat alveolar type II cells (AECII) with PMA, a PKC (protein kinase C) agonist, had no effect on Prdx6 expression but led to approximately 75% increase in aiPLA(2) activity that was abolished by pretreatment of cells with the MAPK (mitogen-activated protein kinase) inhibitors, SB202190 or PD98059. Prdx6 phosphorylation after incubation of AECII with PMA was demonstrated by autoradiography after immunoprecipitation with either anti-phosphothreonine o-phosphoserine antibodies. in vitro, several active isoforms of ERK (extracellular-signal-regulated kinase) and p38 phosphorylated Prdx6, resulting in an 11-fold increase in aiPLA(2) activity. The increased activity was calcium-independent and was abolished by the aiPLA(2) inhibitors, surfactant protein A and hexadecyl-3-trifluorethylglycero-sn-2-phospho-methanol (MJ33). The peroxidase activity of Prdx6 was unaffected by phosphorylation. Mass spectroscopic analysis of in vitro phosphorylated Prdx6 showed a unique phosphorylation site at Thr-177 and mutation of this residue abolished protein phosphorylation and the increase in MAPK-mediated activity. These results show that the MAPKs can mediate phosphorylation of Prdx6 at Thr-177 with a consequent marked increase in its aiPLA(2) activity.
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PMID:Mitogen-activated protein kinase-mediated phosphorylation of peroxiredoxin 6 regulates its phospholipase A(2) activity. 1914 Aug 3

In the present study, the chemopreventive effect of topical application of perillyl alcohol (POH) on 9,10-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis and its possible mechanisms of action in Swiss albino mice were investigated. We evaluated the effect of pretreatment of POH (6 and 12 mg/kg body weight) on TPA (2 microg/200 microl of acetone)-induced skin edema, hyperplasia, peroxidase damage and modulation in activities of catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione contents. Application of POH 30 min prior to TPA treatment, showed a protective effect in almost all the investigated parameters. Additionally, pretreatment with POH showed a significant inhibition of ornithine decarboxylase (ODC) activity and [(3)H] thymidine incorporation into epidermal DNA. In promotion phase, a significant reduction was found in tumor incidence and tumor burden in mice pretreated with POH (12 mg/kg body weight) with extension of the latency period from 4 to 8 weeks as compared to those treated with TPA alone. POH significantly suppressed the Ras/Raf/ERK pathway and induced apoptosis in Swiss albino mice skin. Our findings suggested that the chemopreventive efficacy of POH is probably due to the inhibition of oxidative stress responses, inhibition of the Ras cell proliferation pathway and induction of apoptosis in murine skin tumor promotion phase.
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PMID:Perillyl alcohol attenuates Ras-ERK signaling to inhibit murine skin inflammation and tumorigenesis. 1916 93

The percent weight gain (PWG) and feed efficiency (FE) of Epinephelus coioides were calculated, and the lactobacilli and total microbiota in the posterior intestines, and non-specific immune parameters of grouper, and its susceptibility to Streptococcus sp. and an iridovirus were determined when the fish were fed diets containing Lactobacillus plantarum at 0 (control), 10(6), 10(8), or 10(10) colony-forming units (cfu) kg(-1) for 4 weeks. Results showed that grouper fed a diet containing L. plantarum at the levels of 10(6), 10(8), and 10(10) cfu kg(-1) had significantly increased PGW and FE especially at 10(8) cfu kg(-1) group which were 404.6% and 1.26, respectively. L. plantarum significantly increased in the fish posterior intestines during the L. plantarum feeding period, but decreased rapidly from the intestine within 1 week after changing to the control diet (without L. plantarum). Fish fed a diet containing L. plantarum at 10(6) and 10(8) cfu kg(-1) had significantly higher survival rates than those fed the control diet after challenge with Streptococcus sp., as well as those fed 10(8) cfu kg(-1) after challenge with an iridovirus, causing increases in the survival rates of 23.3%, 20.0%, and 36.7%, respectively, compared to the control group. The alternative complement activity (ACH(50)) level of fish fed diets containing L. plantarum after 4 weeks was significantly higher than that of fish fed the control diet, and that of the 10(8) cfu kg(-1) group was significantly higher than those of the 10(6) and 10(10) cfu kg(-1) groups, which increased by 83.4% compared to the control group. The lysozyme activity and glutathione peroxidase (GPx) activity of fish fed the L. plantarum-containing diets at 10(8) and 10(10) cfu kg(-1) significantly increased compared to those fed the 10(6) cfu kg(-1)L. plantarum diet and control diet, and had increased by 76.3% and 136.6%, and 57.1% and 113.3%, respectively, compared to those fed the control diet. The phagocytic activity (PA), phagocytic index (PI), and respiratory bursts of head kidney leucocytes of fish fed 10(6), 10(8), and 10(10) cfu kg(-1)L. plantarum diets were significantly higher than those of fish fed the control diet after 4 weeks of feeding, and increased 2.2-, 2.2-, and 2.3-fold; 1.8-, 1.8-, and 2.0-fold; and 1.4-, 1.4-, and 1.4-fold, respectively, compared to the control group. We therefore recommend dietary L. plantarum administration at 10(8) cfu kg(-1) to promote growth and enhance immunity and resistance against Streptococcus sp. and an iridovirus of E. coioides.
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PMID:Dietary administration of the probiotic, Lactobacillus plantarum, enhanced the growth, innate immune responses, and disease resistance of the grouper Epinephelus coioides. 1926 34


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