Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heavy metal intoxication of newborn infants fed with "Ba-Pao-Neu-Hwang-San" has been reported every year by many hospitals in Taiwan. About nine years ago, the National Laboratories of Foods and Drugs of the Department of Health, Executive Yuan, received one case report of a five month old female infant who died as a result of long term feeding with "Ba-Pao-Neu-Hwang-San". The drug was found to have contained lead 44,000 ppm. Although this unfortunate incident was propagated by most newspapers, the prescription of this ancient Chinese medicinal preparation is still widely accepted by ordinary people. Herbal medicine doctors prefer complex mineral drugs as did their ancestors thousands of years ago. In the last two years, we have collected 5 samples of "Ba-Pao-Neu-Hwang-San" from different manufacturers and measured the concentration of 16 heavy metals (including Cadmium, Mercury, Arsenic, Lead, Chromium, Manganese, Selenium, Germanium, Nickel, Calcium, Magnesium, Aluminum, Iron, Copper, Zinc, and Vanadium) in these drugs with Inductively-Coupled Plasma Atomic Emission Spectrometry and Graphite Furnace Atomic Absorption Spectrometry. The result of our survey revealed that the first sample (from Tainan) contained mercury 52,800 ppm, the fourth (from Ping-tung) contained mercury 34,500 ppm, and the fifth (from Sin-chu) contained mercury 65,700 ppm. The mercurial contents of these samples were apparently too high to be a safe drug.
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PMID:[Heavy metals in traditional Chinese medicine: ba-pao-neu-hwang-san]. 836 65

Selenium-accumulating Astragalus spp. contain an enzyme which specifically transfers a methyl group from S-methylmethionine to the selenol of selenocysteine, thus converting it to a nontoxic, since nonproteinogenic, amino acid. Analysis of the amino acid sequence of this enzyme revealed that Escherichia coli possesses a protein (YagD) which shares high sequence similarity with the enzyme. The properties and physiological role of YagD were investigated. YagD is an S-methylmethionine: homocysteine methyltransferase which also accepts selenohomocysteine as a substrate. Mutants in yagD which also possess defects in metE and metH are unable to utilize S-methylmethionine for growth, whereas a metE metH double mutant still grows on S-methylmethionine. Upstream of yagD and overlapping with its reading frame is a gene (ykfD) which, when inactivated, also blocks growth on methylmethionine in a metE metH genetic background. Since it displays sequence similarities with amino acid permeases it appears to be the transporter for S-methylmethionine. Methionine but not S-methylmethionine in the medium reduces the amount of yagD protein. This and the existence of four MET box motifs upstream of yfkD indicate that the two genes are members of the methionine regulon. The physiological roles of the ykfD and yagD products appear to reside in the acquisition of S-methylmethionine, which is an abundant plant product, and its utilization for methionine biosynthesis.
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PMID:S-methylmethionine metabolism in Escherichia coli. 988 84

To determine if elevated concentrations of waterborne selenium (Se), caused by coal mining, in the Elk River in southeastern British Columbia, may be causing reproductive or teratogenic effects in wild cutthroat trout (Oncorhynchus clarki lewisi), fertilized eggs from exposed and reference fish were raised in the laboratory. Eggs from each female were reared separately and the percent mortalities and deformities were related to the selenium content of the eggs. Selenium concentrations in females from the exposed site were highest in the liver (36.6 +/- 22.5 microg/g dry weight, range: 18.3 to 114), followed by the eggs (21.0 +/- 18.3 microg/g, range: 8.7 to 81.3) and the muscle (12.5 +/- 7.7 microg/g, range: 6.7 to 41). Despite these elevated egg Se concentrations, there was no significant effect on fertilization; time to hatch; percent hatch; or egg, larvae, and fry deformities or mortalities. Reproductive failure and embryonic terata have been reported at much lower egg Se concentrations in other fish species. The lack of any toxic response in this study may be due to an evolved tolerance to higher tissue Se concentrations in a population of fish living in a seleniferous river system.
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PMID:The effect of bioaccumulated selenium on mortalities and deformities in the eggs, larvae, and fry of a wild population of cutthroat trout (Oncorhynchus clarki lewisi). 1191 51

Reactive oxygen species (ROS) during normal metabolism signal cells to stimulate proliferation or to cause cellular damages, depending on a specific concentration. Energy restriction (ER) increases life span in animals, which can explain an effective modulator for reducing oxidative stress. Oxidative stress can result from a decrease in the protection against ROS. The deleterious effects of oxidative stress generally occur after exposure to a relatively high concentration of ROS. Alternatively, it has been suggested that a low concentration of ROS can exert important physiological roles in cellular signaling and proliferation. Signal pathways are crucial for cell survival or death. It is generally acceptable that aged cells have less response to stresses such as ROS than young cells. Oxidative stresses induce JNK and p38 kinase pathways regulated by redox regulatory proteins: thioredoxin and glutathione s-transferase, respectively. Antioxidants such as selenium block apoptosis induced by ROS through blocking apoptotic signal ASK1 and stimulating survival signal Akt activity. Old hepatocytes are more susceptible to ROS-induced apoptosis than young hepatocytes, which is associated with low expression of ERK and Akt kinases. Pharmacological inhibition of ERK and Akt activation in the young cells markedly increase their sensitivity to H(2)O(2), and ER, by preventing loss of ERK and Akt activities, enhances survival of old hepatocytes to a level similar to those of young cells. Expressions of signal pathways such as survival and apoptotic signals can regulate cells' fate and aging process. Further studies on the interaction of signal pathways may change the scientific direction of the study of aging.
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PMID:Dose effect of oxidative stress on signal transduction in aging. 1247 Aug 97

The ischemic-reperfusion syndrome significantly influences the function of a kidney transplanted from a non-heart-beating donor (NHBD). The animal model of a NHBD was used to monitor the influence of exogenous addition of selenium into the reperfusion solution (HTK, Custodiol) with respect to the formation of free oxygen radicals at 0 to 120 minutes after the NHBD transplantation. This maneuvers produced a statistically significant decrease in malondialdehyde concentration, an indicator of free oxygen radicals in the venous blood of the transplanted kidney. The augmentation of the antioxidative capacity of the preservation solution might be a possible route to improve the function of kidneys transplanted from NHBDs.
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PMID:Can the ischemia-reperfusion syndrome in transplanted kidneys procured from non-heart-beating donors be influenced by adding selenium into the reperfusion solution? An experimental study. 1282 26

Ischemia-reperfusion syndrome significantly influences the function of a kidney transplanted from a non-heart-beating donor (NHBD). An animal model of NHBD was used to monitor the influence of the exogenous addition of selenium in the perfusion solution (HTK, Custodiol) on the generation of free oxygen radicals between 0 and 120 minutes after transplantation of the NHBD organ. During this interval, the malondialdehyde concentration, an indicator of free oxygen radicals in the venous blood of the transplanted kidney, significantly decreased. The augmentation of the anti-oxidant capacity of the preservation solution might represent a possible improvement in the function of kidneys transplanted from NHBDs.
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PMID:Can ischemia-reperfusion syndrome in transplanted kidneys procured from non-heart-beating donors be influenced by adding selenium into the reperfusion solution? An experimental study. 1469 94

Selenium is an essential trace element and is required for the synthesis of cellular enzymes that protect against oxidative stress. Epidemiological findings indicate that low selenium intake is associated with increased cancer risk, and, although the majority of studies show that exposure of transformed cells to selenium results in apoptotic cell death, there are reports indicating that cells exposure to low selenium concentrations promotes cellular proliferation. Gastric adenocarcinoma SNU-1 cells responded to selenomethionine with a biphasic proliferative curve: enhanced incorporation of 3H-thymidine into DNA within a very narrow range of selenomethionine concentrations followed by decreased 3H-thymidine uptake at higher levels. Concentrations of selenomethionine that stimulate cellular proliferation also induce cellular oxidation and phosphorylation of MAPK (ERK), a component of cell signaling cascades. MAPK (ERK) phosphorylation is synonymous with MAPK activation and enhanced cell growth. Our findings support previous observations of enhanced proliferation in response to low levels of selenium and suggest that, at certain concentrations, selenomethionine induces mild oxidative stress that, in turn, stimulates DNA synthesis.
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PMID:Selenomethionine stimulates MAPK (ERK) phosphorylation, protein oxidation, and DNA synthesis in gastric cancer cells. 1548 2

Selenium has been found at elevated concentrations in water, sediments, and aquatic biota in the Elk River (British Columbia, Canada) and some of its tributaries downstream of several coal mines. Selenium water concentrations in those areas exceed Canadian and British Columbia guidelines and are above levels at which adverse effects to fish and waterfowl could occur. We compared selenium concentrations in the eggs of two riverine waterbirds, American dippers and spotted sandpipers, with measures of productivity: the number of eggs laid, egg hatchability, and nestling survival. In American dippers, the mean egg selenium concentration from the exposed areas, 1.10 +/- SE 0.059 microg/g wet weight, was indistinguishable from the reference areas, 0.96 +/- SE 0.059 microg/g wet weight. For spotted sandpipers, the mean egg selenium concentration in the exposed areas, 2.2 +/- 0.5 microg/g wet weight, was significantly higher than in the reference areas, 1.2 +/- 0.14 microg/g wet weight, but less than reported thresholds for waterfowl and other shorebirds. There were no significant differences in egg hatchability between dippers in reference and exposed areas, but reduced hatchability was apparent for sandpipers in exposed locations. Despite the slightly reduced hatchability in sandpipers, overall productivity was higher than regional norms for both species; thus, selenium did not affect the number of young recruited to local populations. We did not observe teratogenic effects in either species, although none was expected at these concentrations. Despite moderately high selenium concentrations in the water, mean egg selenium concentrations were less than predicted from uptake models. We hypothesise that the relatively low uptake of selenium into the eggs of the two waterbirds in this study is likely due to their lotic environment's low biological transformation and uptake rates.
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PMID:Accumulation of selenium and lack of severe effects on productivity of American dippers (Cinclus mexicanus) and spotted sandpipers (Actitis macularia). 1575 Jul 73

Selenium (Se) is an essential micronutrient, exhibiting a narrow margin between nutritionally optimal and potentially toxic concentrations. Egg-laying vertebrates at the top of aquatic food chains are most at risk in environments with elevated aqueous Se concentrations. The Elk River watershed in British Columbia, Canada receives effluents containing Se from five coal mine operations. This study tested three hypotheses that might account for higher Se concentrations in fish from lentic compared to lotic habitats in the watershed: (1) enhanced uptake by aquatic primary producers, (2) longer food chain length, or (3) greater food web accumulation through sediment-detrital pathways. Stable isotope and Se concentration data demonstrated that Se concentrations in aquatic primary producers and food chain lengths were comparable in lentic and lotic habitats. Enhanced formation of organoselenium and subsequent uptake and cycling via sediment detrital pathways likely account for higher fish tissue Se concentrations in lentic than in lotic areas.
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PMID:Food chain transfer of selenium in lentic and lotic habitats of a western Canadian watershed. 1627 61

Prevention trials showed that selenium reduced prostate cancer incidence by 50%, establishing selenium as a promising chemopreventive agent for prostate cancer. Selenium inhibited human prostate cancer cell growth, blocked cell cycle progression at multiple transition points, and induced apoptotic cell death. Previous studies showed a novel mechanism of selenium anticancer action in which selenium markedly reduces androgen signaling and androgen receptor (AR)-mediated gene expression, including prostate-specific antigen (PSA), in human prostate cancer cells. The molecular mechanisms of selenium-mediated down-regulation of AR signaling are not clear. In this study, a systemic approach was taken to examine the modification of androgen signaling by selenium in human prostate cancer cells. In addition to reduced AR mRNA expression, selenium was found to initially increase the stability of AR mRNA within 6 hours while decreasing the stability of AR mRNA after 8 hours. Selenium increased AR protein degradation and reduced AR nuclear localization. Scatchard analysis indicated that selenium did not affect ligand binding to AR in LNCaP cells. Chromatin immunoprecipitation analyses showed that DHT increased the recruitment of AR and coactivators, such as SRC-1 and TIF-2, to the promoter of the PSA gene, and that recruitment was greatly diminished in the presence of 5 micromol/L selenium. On the other hand, selenium enhanced the recruitment of corepressors, such as SMRT, to the promoter of the PSA gene. Taken together, these results suggest that selenium disrupts AR signaling at multiple stages, including AR mRNA expression, mRNA stability, protein degradation, nuclear translocation, and recruitment of coregulators.
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PMID:Mechanisms of selenium down-regulation of androgen receptor signaling in prostate cancer. 1664 61


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