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

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Humans are exposed occupationally and environmentally to metal aerosols including lead (Pb2+) and cadmium (Cd2+). These toxicants accumulate in male reproductive organs. Epidemiological studies have been equivocal about effects of Pb2+ and Cd2+ on hormone concentrations, male fertility and sperm parameters. Comparison of Pb2+ and Cd2+ concentrations in fertile and infertile men are problematic. Problem areas include failure to control confounding variables, but genetic polymorphisms as in somatic diseases may modulate Pb2+ and Cd2+ damage. Multiple calcium (Ca2+) and potassium (K+) channel isoforms have been identified in human testes and spermatozoa. These Ca2+ and K+ channels are involved in early events of acrosome reactions. Ca2+ channel are susceptible to Cd2+ poisoning and K+ channels to Pb2+. These channels offer entry paths for metallic toxicants into mature spermatozoa. Ion channel polymorphisms may cause differential sensitivities to Cd2+ and Pb2+, explaining in part prospective blinded studies showing high Cd2+ in varicocele-related human infertility and high Pb2+ in unexplained infertility. In both forms of male infertility the ability to undergo an acrosome reaction decreases. Reverse transcriptase-polymerase chain reaction assays for Ca2+ and K+ channel isoforms may identify susceptibility subgroups with lower resistance to environmental exposures.
...
PMID:Male infertility and environmental exposure to lead and cadmium. 1078 69

Reverse transcriptase-polymerase chain reaction has been used to isolate one metallothionein isoform (MT-20) complementary DNA from RNA extracted from mussel gill. Another cDNA, isolated by screening a Mytilus edulis cDNA mantle library using the first cDNA as probe, codes for the MT-10 IV isoform. Northern blot analysis using these cDNAs revealed different expression of these isoforms. Induction with CdC1(2) caused high levels of both MT messenger RNAs, especially the MT-20, which was induced by cadmium salt but not by zinc and copper salts. An induction of MT-10 was detected with ZnCl(2). These results show that genes encoding distinct MT isoforms are differentially regulated by heavy metals.
...
PMID:Metallothionein Isoforms in Mytilus edulis (Mollusca, Bivalvia): Complementary DNA Characterization and Quantification of Expression in Different Organs after Exposure to Cadmium, Zinc, and Copper. 1081 60

In the search for P2-receptors modulating the stimulation-evoked entry of calcium at processes of PC12 cells differentiated in the presence of nerve growth factor and neurotrophin-3, electrically evoked increases in free calcium were assessed by fura-2 microfluorimetry. Omission of calcium and addition of cadmium (100 microM) or the N-type calcium channel blocker omega-conotoxin GVIA (0.5 microM) abolished or markedly reduced the evoked responses. The P2Y-receptor agonists 2-methylthio adenosine 5'-diphosphate (2-methylthio-ADP), ADP, and adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS) inhibited the electrically evoked entry of calcium without any changes in basal calcium concentrations. 2-Methylthio-ADP was the most potent agonist. Adenosine, P(1),P(4)-di(adenosine-5')-tetraphosphate (Ap4A), UDP, and UTP (30 microM each) had no effect. The effect of ADPbetaS (30 microM) was abolished by the P2-antagonists reactive blue 2 (3 microM), suramin (100 microM), 2-methylthio-AMP (10 microM), p-chloromercuriphenyl sulfonic acid (1 microM), and AR-C 69931MX [N(6)-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma-dichloromethylene adenosine 5'-triphosphate] (300 nM). In contrast, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (10 microM), the selective P2Y1-receptor antagonist MRS 2179 (N(6)-methyl-2'-deoxyadenosine 3',5'-bisphosphate; 10 microM), as well as the adenosine A(1)-receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine; 100 nM), caused no change. Pretreatment with pertussis toxin abolished the effect of ADPbetaS. Reverse transcriptase-polymerase chain reaction revealed the presence of mRNA for P2Y12-receptors in nondifferentiated and differentiated PC12 cells. The results indicate that processes of differentiated PC12 cells possess P2Y12-receptors coupling to pertussis toxin-sensitive G-proteins and mediating an inhibition of the stimulation-evoked entry of calcium through omega-conotoxin GVIA-sensitive calcium channels. This suggests a role of P2Y12-receptors in neuromodulation in addition to their involvement in platelet aggregation.
...
PMID:P2Y-receptors mediating an inhibition of the evoked entry of calcium through N-type calcium channels at neuronal processes. 1238 31

The response of a metal tolerant plant to heavy metal stress involves a number of biochemical pathways. To investigate the overall molecular response of a metal-tolerant plant to heavy-metal exposure, suppressive subtractive hybridization was used to create a library enriched in cadmium-induced cDNAs from cadmium-tolerant Datura innoxia. Two differential screening steps were used to screen the cadmium-induced library resulting in 8 putative cadmium-specific cDNAs out of a pool of 94 clones. Reverse transcriptase polymerase chain reaction was used to confirm that 4 of these 8 clones were cadmium-specific, while the other 4 were induced under heat shock or in the no treatment cells in addition to cadmium exposure. All 8 cDNAs were sequenced and used to search for identification against GenBank. One of the 4 cadmium-specific cDNAs had homology to a sulfur transferase-family protein in Arabidopsis thaliana. The possible link between this result and the heavy-metal response of plants is discussed.
...
PMID:Gene expression in cadmium-tolerant Datura innoxia: detection and characterization of cDNAs induced in response to Cd2+. 1282 91

The yvgW gene of Bacillus subtilis has been reported to encode a product which resembles CPx-type ATPase having a function related to Cd2+ and Zn2+ resistance through efflux of this metal. We recently showed that yvgW gene product is also important for sporulation in B. subtilis. The present study was focused on the functional characterization of yvgW in the sporulation process of B. subtilis. The analysis of yvgW expression showed that a significant expression took place during the late stage of sporulation (T5-T8). The deletion of spoIIAC and spoIIGB genes, encoding for sigmaF and sigmaE, respectively, resulted in the complete elimination of yvgW-lacZ expression while the deletion of the spoIIIG coding for sigmaG decreased the yvgW-lacZ expression to only 37% that of the wild type level. In contrast, the deletion of spoIVCB gene coding for sigmaK had no significant effects on the yvgW-lacZ expression. Transcription initiation site of yvgW during sporulation was determined by 5'-RACE-PCR, indicating that -10 and -35 sequences exhibited very good homology with the consensus sequences recognized by RNA polymerase containing sigmaE. Moreover, through the construction of yvgWDelta537-1351::spc, yvgW mutant cells were investigated for their spore properties, such as their resistance profiles against heat, chloroform and lysozyme, pointing out that spores of the mutant cells showed high sensitivity to heat and chloroform, but resistance to lysozyme. The level of dipicolinic acid was also significantly reduced to approximately 63% in yvgW spores as compared to wild type spores. Furthermore, the analyses of the nutrition-specific germination and outgrowth characteristics of the null mutant and the wild type cells revealed no defect in the initiation of yvgW spore germination but they returned to vegetative state more slowly than the wild type spores in minimal medium.
...
PMID:Sporulation-specific expression of the yvgW (cadA) gene and the effect of blockage on spore properties in Bacillus subtilis. 1690 59

The production of polysaccharide intercellular adhesin (PIA) is an essential process in foreign body infections mediated by Staphylococcus epidermidis. Transcriptional regulation of the icaADBC operon, the genes responsible for production of enzymes that synthesize PIA, is multi-factorial and involves at least SarA and sigmaB. Transcriptional and promoter fusion studies revealed that the decreased transcription of the icaADBC operon observed in a S. epidermidis 1457 sigB mutant is not mediated through a direct interaction of sigmaB-RNA polymerase at the icaADBC promoter region but instead through the upregulation of IcaR, a known repressor of icaADBC transcription. Transcriptional analysis of a 1457 sigB-icaR double mutant confirmed that the decreased icaADBC transcript in 1457 sigB is IcaR dependent. Furthermore, primer extension studies suggest that the icaR promoter appears to be sigmaA dependent, suggesting that sigmaB indirectly controls icaR transcription through an unknown pathway. In addition, it was confirmed that the loss of SarA results in the loss of icaADBC transcription and PIA production in S. epidermidis. It was further demonstrated, through the over-production of SarA in 1457 sigB, that the loss of sarP1 promoter activity in 1457 sigB has little or no effect on the loss of PIA production in this mutant. Finally, it was demonstrated that PIA production could be restored in both 1457 sigB and 1457 sarA by complementing these mutants with a full-length icaADBC operon controlled by a cadmium-inducible noncognate promoter. It is concluded that sigmaB and SarA operate independently of each other to regulate PIA production and biofilm development in S. epidermidis.
...
PMID:SigmaB and SarA independently regulate polysaccharide intercellular adhesin production in Staphylococcus epidermidis. 1749 53

A chloride current, I(Cl,H), slowly activating on hyperpolarisation was investigated in Drosophila melanogaster larval muscles using the two-electrode voltage clamp. Sizeable currents were observed after the intracellular chloride concentration ([Cl-]i) had been elevated by diffusion of Cl- from the electrodes. The time course of I(Cl,H) was rather variable and required two exponentials to be accurately described. The reversal potential, -40 to -20 mV in Cl- -loaded fires, shifted on lowering external [Cl-] in the positive direction. Steady-state activation of I(Cl,H) was characterised by V0.5 of approximately -120 mV and a slope factor, k, of approximately 10 mV at a [Cl-]i approximately 35 mmol l(-1). Raising [Cl-]i to approximately 50 mmol l(-1) caused a negative shift of V0.5 equivalent to the change of E(Cl) and led to a nearly threefold increase in maximal steady-state conductance. I(Cl,H) was resistant to 10 mmol l(-1) Zn2+ and 1 mmol l(-1) Cd2+ but was greatly reduced by 1 mmol l(-1) 9-anthracenecarboxylic acid (9-AC). I(Cl,H) was affected by changes of extracellular pH and increased on lowering extracellular osmolality. 9-AC also decreased muscle fibre resting conductance by approximately 20% and increased muscle contractions. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the expression of all three ClC genes in muscle, and immunohistochemistry indicated location of Drosophila melanogaster chloride channel-2 (DmClC-2) at the Z-lines. We conclude that DmClC-2 accounts for the channels underlying I(Cl,H), and in part for the resting chloride conductance. DmClC-2 may serve general homeostatic mechanisms such as pH- and osmo-regulation or may support muscle function on high motor activity or during a particular neurohormonal state of the animal.
...
PMID:Properties and possible function of a hyperpolarisation-activated chloride current in Drosophila. 1760 53

Cadmium (Cd) exposure results in injury to the proximal tubule characterized by polyuria and proteinuria. Kidney injury molecule-1 (Kim-1) is a transmembrane glycoprotein not normally detected in the mature kidney, but is upregulated and shed into the urine following nephrotoxic injury. In this study, we determine if Kim-1 might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. Weekly urine samples were analyzed for Kim-1, protein, creatinine, metallothionein, and Clara cell protein CC-16. Significant levels of Kim-1 were detected in the urine by 6 weeks and continued to increase throughout the treatment period. This appearance of Kim-1 occurred 4-5 weeks before the onset of proteinuria, and 1-3 weeks before the appearance of metallothionein and CC-16. Higher doses of Cd gave rise to higher Kim-1 excretion. Reverse transcriptase-polymerase chain reaction (RT-PCR) expression analysis showed that Kim-1 transcript levels were increased after 6 weeks at the low dose of Cd. Immunohistochemical analysis showed that Kim-1 was present in proximal tubule cells of the Cd-treated rats. Our results suggest that Kim-1 may be a useful biomarker of early stages of Cd-induced proximal tubule injury.
...
PMID:Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity. 1768 58

Arabidopsis thaliana acyl-CoA-binding protein 2 (ACBP2) was observed to interact with farnesylated protein 6 (AtFP6), which has a metal-binding motif (M/LXCXXC). Their interaction and expression in response to heavy metals were investigated. Yeast two-hybrid analysis and in vitro assays showed that an ACBP2 derivative lacking ankyrin repeats did not interact with AtFP6, indicating that the ankyrin repeats mediate protein-protein interaction. Autofluorescence-tagged ACBP2 and AtFP6 transiently co-expressed in tobacco (Nicotiana tabacum) were both targeted to the plasma membrane. Reverse transcriptase polymerase chain reaction and northern blot analyses revealed that AtFP6 mRNA was induced by cadmium (Cd(II)) in A. thaliana roots. Assays using metal-chelate affinity chromatography demonstrated that in vitro translated ACBP2 and AtFP6 bound lead (Pb(II)), Cd(II) and copper (Cu(II)). Consistently, assays using fluorescence analysis confirmed that (His)(6)-AtFP6 bound Pb(II), like (His)(6)-ACBP2. Arabidopsis thaliana plants overexpressing ACBP2 or AtFP6 were more tolerant to Cd(II) than wild-type plants. Plasma membrane-localized ACBP2 and AtFP6 probably mediate Pb(II), Cd(II) and Cu(II) transport in A. thaliana roots. Also, (His)(6)-ACBP2 binds [(14)C]linoleoyl-CoA and [(14)C]linolenoyl-CoA, the precursors for phospholipid repair following lipid peroxidation under heavy metal stress at the plasma membrane. ACBP2-overexpressing plants were more tolerant to hydrogen peroxide than wild-type plants, further supporting a role for ACBP2 in post-stress membrane repair.
...
PMID:Arabidopsis thaliana acyl-CoA-binding protein ACBP2 interacts with heavy-metal-binding farnesylated protein AtFP6. 1882 12

Caulobacter crescentussigma(E) belongs to the ECF (extracytoplasmic function) subfamily of RNA polymerase sigma factors, whose members regulate gene expression in response to distinct environmental stresses. During physiological growth conditions, data indicate that sigma(E) is maintained in reduced levels due to the action of ChrR, a negative regulator of rpoE gene expression and function. However, once bacterial cells are exposed to cadmium, organic hydroperoxide, singlet oxygen or UV-A irradiation, transcription of rpoE is induced in a sigma(E)-dependent manner. Site-directed mutagenesis indicated that residue C188 in ChrR is critical for the cadmium response while residues H140 and H142 are required for the bacterial response to organic hydroperoxide, singlet oxygen and UV-A. Global transcriptional analysis showed that sigma(E) regulates genes involved in protecting cells against oxidative damages. A combination of transcriptional start site identification and promoter prediction revealed that some of these genes contain a putative sigma(E)-dependent motif in their upstream regions. Furthermore, deletion of rpoE and two sigma(E)-dependent genes (cfaS and hsp20) impairs Caulobacter survival when singlet oxygen is constantly generated in the cells.
...
PMID:The transcriptional response to cadmium, organic hydroperoxide, singlet oxygen and UV-A mediated by the sigmaE-ChrR system in Caulobacter crescentus. 1940 Aug 3


<< Previous 1 2 3 Next >>

---