Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, cDNA and genomic clones encoding a homologue of the yeast gene anti-oxidant 1 (ATX1) from the white-rot fungus Trametes versicolor, a basidiomycete known to produce several laccase isoenzymes involved in lignin degradation, were identified. This gene, named Trametes ATX homologue (tahA), encodes a protein of 7.9 kDa with 56% identity to the yeast Atx1p sequence. Two different alleles of tahA were obtained that differed mainly in their intervening sequences and in a 425 nt insertion located 183 nt upstream of the transcription start site. tahA is present as one copy per haploid nucleus in T. versicolor, as shown by Southern analysis. Expression of tahA cDNA restored high-affinity iron uptake in a deltaatx1 yeast strain and oxygen sensitivity in a deltasod1 deltasod2 yeast strain, showing that tahA is also a functional homologue of ATX1. The inability of tahA to rescue the deltasod1 phenotype on copper-deficient medium indicated that tahA function is copper-dependent. Sequence analysis of the tahA promoter revealed several motifs that were similar to the conserved motifs found in the copper-regulated metallothionein and Cu, Zn superoxide dismutase genes, CUP1 and SOD1, of Saccharomyces cerevisiae, Neurospora crassa and Candida glabrata. In contrast to its yeast homologue ATX1, tahA is induced under elevated copper concentrations in the medium (>0.25 micro M CuSO(4)) and repressed under copper starvation. The transcription of tahA was analysed in response to copper and iron, and after adding xenobiotica. The results are discussed in relevance to laccase expression.
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PMID:Identification and functional expression of tahA, a filamentous fungal gene involved in copper trafficking to the secretory pathway in Trametes versicolor. 1248 Sep 8

Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, and renal failure. We had proposed that a common set of transcriptional adaptations underlie the loss of muscle mass in these different states. To test this hypothesis, we used cDNA microarrays to compare the changes in content of specific mRNAs in muscles atrophying from different causes. We compared muscles from fasted mice, from rats with cancer cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal nephrectomy, and from pair-fed control rats. Although the content of >90% of mRNAs did not change, including those for the myofibrillar apparatus, we found a common set of genes (termed atrogins) that were induced or suppressed in muscles in these four catabolic states. Among the strongly induced genes were many involved in protein degradation, including polyubiquitins, Ub fusion proteins, the Ub ligases atrogin-1/MAFbx and MuRF-1, multiple but not all subunits of the 20S proteasome and its 19S regulator, and cathepsin L. Many genes required for ATP production and late steps in glycolysis were down-regulated, as were many transcripts for extracellular matrix proteins. Some genes not previously implicated in muscle atrophy were dramatically up-regulated (lipin, metallothionein, AMP deaminase, RNA helicase-related protein, TG interacting factor) and several growth-related mRNAs were down-regulated (P311, JUN, IGF-1-BP5). Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases.
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PMID:Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. 1471 85

Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in the presence of leukemia inhibitory factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38alpha mitogen-activated protein kinase (MAPK) activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at 3 days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene, which prevents apoptosis of early differentiated cells.
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PMID:Apoptosis and differentiation commitment: novel insights revealed by gene profiling studies in mouse embryonic stem cells. 1631 15

Some effects of cadmium exposure (100 microg/L for 4, 8, 12, and 24 h) on the estuarine polychaete Laeonereis acuta (Nereididae) were evaluated. This polychaete was able to accumulate cadmium in the body, with the metal stored mainly in the cytosolic fraction (>10 kDa). Activity of the antioxidant enzymes superoxide dismutase, glutathione S-transferase, and glutathione reductase (GR) as well as the total oxyradical scavenger capacity, the glutamate cysteine ligase catalytic subunit gene expression, and the metallothionein-like proteins content were not affected by cadmium at any exposure time tested. Catalase (CAT) activity, however, was significantly lower (p < 0.05) in worms treated with cadmium compared with that in controls after 8 h of exposure. At the same exposure time, lipid peroxide levels were increased (p < 0.05) in worms exposed to cadmium compared with those in control worms. Interestingly, CAT and GR activities decreased over time (p < 0.05) independent of cadmium treatment, which is a result that could be attributed to starvation. The effects caused by cadmium in the present study were observed only after 8 h of exposure, demonstrating that cadmium can generate oxidative stress.
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PMID:Short-term responses to cadmium exposure in the estuarine polychaete Laeonereis acuta (polychaeta, Nereididae): subcellular distribution and oxidative stress generation. 1670 67

Metallothioneins are low molecular weight polypeptides, present in most eukaryotic phyla, with role in metal homeostasis and detoxification. We previously reported the identification and the characterization of a metallothionein gene (GmarMT1) from the arbuscular mycorrhizal fungus Gigaspora margarita. Here, we have used real-time quantitative RT-PCR to show that GmarMT1 expression was turned off during the symbiotic fungal growth in the hexose-rich mycorrhizal apoplast, whereas transcripts were abundant during all other fungal growth stages, when products of lipid breakdown and the glyoxylate cycle feed carbohydrate-consuming pathways. In support of a nutritional regulation of GmarMT1 expression, we show that transcriptional activity of GmarMT1 promoter in yeast was strongly induced by glucose starvation (up to 20 times the basal level). We speculate that GmarMT1-encoded protein, with its proved metal binding ability, could regulate the homeostasis of zinc, a fundamental cofactor involved in C metabolism regulation and glucose repression.
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PMID:Enhanced activity of the GmarMT1 promoter from the mycorrhizal fungus Gigaspora margarita at limited carbon supply. 1748 90

Nutrigenomics examines nutrient-gene interactions on a genome-wide scale. Increased dietary fat or higher non-esterified fatty acids (NEFA) from starvation-induced mobilisation may enhance hepatic oxidation and decrease esterification of fatty acids by reducing the expression of the fatty acid synthase gene. The key factors are the peroxisome proliferator-activated receptors (PPARs). Dietary carbohydrates--both independently and through insulin effect--influence the transcription of the fatty acid synthase gene. Oleic acid or n-3 fatty acids downregulate the expression of leptin, fatty acid synthase and lipoprotein lipase in retroperitoneal adipose tissue. Protein-rich diets entail a shortage of mRNA necessary for expression of the fatty acid synthase gene in the adipocytes. Conjugated linoleic acids (CLAs) are activators of PPAR and also induce apoptosis in adipocytes. Altered rumen microflora produces CLAs that are efficient inhibitors of milk fat synthesis in the mammary gland ('biohydrogenation theory'). Oral zinc or cadmium application enhances transcription rate in the metallothionein gene. Supplemental CLA in pig diets was found to decrease feed intake and body fat by activating PPARgamma-responsive genes in the adipose tissue. To prevent obesity and type II diabetes, the direct modulation of gene expression by nutrients is also possible. Nutrigenomics may help in the early diagnosis of genetically determined metabolic disorders and in designing individualised diets for companion animals.
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PMID:Veterinary aspects and perspectives of nutrigenomics: a critical review. 1755 88

Gulf annual ryegrass has been identified as potential Pi hyperaccumulator, however the molecular mechanism remains largely unknown. A suppression subtractive hybridization (SSH) analysis was used to evaluate the phosphate (Pi) responsive genome expression pattern changes in Gulf annual ryegrass (Lolium multiflorum L.). Differential screening identified 384 putative Pi-starvation induced cDNAs. Bioinformatic analysis revealed that 116 cDNAs are nonredundant unigenes of which 108 exhibited high similarities with Genbank entries. The differential expression patterns of 13 cDNAs, representing diverse functional categories, were confirmed by RNA gel blot analysis. Further, detailed molecular analysis of three genes (LmPAP1, LmIPS1 and LmIDS1) was carried out by cloning and characterization of full-length cDNAs. LmPAP1 is 1,414 bp in length with an open reading frame (ORF) of 1,188 bp capable of encoding an N-terminal signal peptide of 26 amino acids. LmIPS1 gene is a member of TPSI1/Mt4 family that contains 3 short ORFs. The cDNA of LmIDS1 is 346 bp in size including a single ORF of 222 nucleotides that encodes 74 amino acid proteins, exhibiting homology with IDS1 with similarity to type 2 metallothionein like protein. In our preliminary screening of different genotypes of annual ryegrass for hyperaccumulation of Pi in their shoots, Gulf and Urugrary showed significant differences with values of 1.0% and 0.7%, respectively. Since it is logical to assume a plausible correlation that may exist between Pi-accumulation in the shoots and the expression of Pi-responsive genes, the expression of LmPAP1, LmIPS1 and LmIDS1 was evaluated in these two genotypes grown under different Pi regimes. Although there was a significant induction of these genes in both the genotypes grown under Pi-deprived condition, the abundance of LmPAP1 transcripts was relatively higher in the Gulf genotype as compared to that in the Urugrary genotype. A similar trend was observed in qRT-PCR data of other tested genotypes of annual ryegrasses. This suggests the potential role of LmPAP1 in accumulation of Pi in Gulf grass. In addition, Gulf grass genotype revealed higher levels of total P, (33)Pi uptake, and APase activity as compared to Urugrary. Together, these results suggest that the Gulf ryegrass has evolved mechanisms to acquire and hyperaccumulate more Pi under different Pi regimes by activating multiple Pi acquisition and mobilization mechanisms.
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PMID:Molecular cloning and characterization of phosphate (Pi) responsive genes in Gulf ryegrass (Lolium multiflorum L.): a Pi hyperaccumulator. 1882 Oct 59

Copper is an integral part of a number of proteins and thus an essential trace metal. However, free copper ions can be highly toxic and every organism has to carefully control its bioavailability. Eukaryotes contain three copper chaperones; Atx1p/Atox1 which delivers copper to ATP7 transporters located in the trans-Golgi network, Cox17 which provides copper to the mitochondrial cytochrome c oxidase, and CCS which is a copper chaperone for superoxide dismutase 1. Here we describe the knockout phenotype of the Drosophila homolog of mammalian Atox1 (ATX1 in yeast). Atox1-/- flies develop normally, though at reduced numbers, and the eclosing flies are fertile. However, the mutants are unable to develop on low-copper food. Furthermore, the intestinal copper importer Ctr1B, which is regulated by copper demand, fails to be induced upon copper starvation in Atox1-/- larvae. At the same time, intestinal metallothionein is upregulated. This phenotype, which resembles the one of the ATP7 mutant, is best explained by intestinal copper accumulation, combined with insufficient delivery to the rest of the body. In addition, compared to controls, Drosophila Atox1 mutants are relatively insensitive to the anticancer drug cisplatin, a compound which is also imported via Ctr1 copper transporters and was recently found to bind mammalian Atox1.
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PMID:Distorted copper homeostasis with decreased sensitivity to cisplatin upon chaperone Atox1 deletion in Drosophila. 2146 78

Metal-responsive transcription factor-1 (MTF-1) is a zinc finger protein conserved from mammals to insects. It mediates protection against heavy metal load by activating the expression of metallothionein and other genes. In Drosophila, MTF-1 serves a dual function in that it not only helps to protect against heavy metal load but also induces the expression of Ctr1B, the gene for an intestinal copper importer, upon copper starvation. By dissecting Drosophila MTF-1 function, we have identified determinants for nuclear import and export, and characterized a phosphorylation site mutant (T127A) that differentially affects MTF-1 target genes. Further, by generating a series of fusion proteins with the heterologous DNA binding domain of Gal4 we identified a strong, constitutive activation domain in the central region of MTF-1 (aa 352-540). By contrast, an extended fusion protein that includes MTF-1's C-terminus (aa 352-791) is not active in standard conditions but induced by copper load. The paramount regulatory importance of the C-terminal part, that harbors a cysteine-rich "metallothionein-like" domain, was corroborated by different experiments. Transgenic flies expressing C-terminally truncated MTF-1 variants displayed high constitutive transcription of both, the genes for metallothioneins and the copper importer Ctr1B. The indiscriminate activation of these genes that are normally induced under opposite conditions of copper load and copper starvation manifested itself in a shortened lifespan, crippled wings, and female sterility.
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PMID:Dissection of Drosophila MTF-1 reveals a domain for differential target gene activation upon copper overload vs. copper starvation. 2213 26

An indoor exposure experiment with juvenile Babylonia areolata was conducted to study its survival, growth, cadmium (Cd) accumulation, metallothionein (MT) induction, and glycogen content as well as the DNA integrity of hepatopancreas tissue. The juveniles were starved or fed with mussel (Perna viridis) or clamworm (Perinereis aibuhitensis), and exposed to 50 microg x L(-1) of Cd2+ for 10 weeks. Prolonged starvation and simultaneous exposure to Cd reduced the survival rate of B. areolata, and its glycogen was mobilized in great extent. Feeding with P. viridis or P. aibuhitensis helped the B. areolata to combat Cd toxicity and lessen mortality. After exposed to Cd, the damage of the DNA integrity of hepatopancreas tissue for the B. areolata fed with P. viridis or P. aibuhitensis could be recovered with time, but not for the starved B. areolata. Prolonged starvation caused tissue atrophy and led to Cd accumulation and MT increase, while feeding with P. viridis or P. aibuhitensis increased the B. areolata mass and lowered the Cd accumulation and MT level because of the tissue dilution effect. The B. areolata fed with P. viridis had better growth and lower Cd content than that fed with P. aibuhitensis. This study indicated that starvation intensified the toxicity of Cd to B. areolata, while prey type had significant effects on the growth rate of the B. areolata and indirectly affected its Cd accumulation, MT induction, and glycogen consumption. It was suggested that when using gastropods such as B. areolata as the indicator species to monitor marine environmental pollution, it would be necessary to consider the effects of habitat ecological data including food richness and prey type. Moreover, in the high-density cultivation of B. areolata in factory, rational feeding and periodic measurement of Cd concentration in seawater should be made.
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PMID:[Cadmium bioaccumulation and its toxicity in Babylonia areolata under different nutritional status]. 2317 75


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