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At least 1,063 records · Page 59Linked to original sources
PubMed2002

APC-dependent regulation of ornithine decarboxylase in human colon tumor cells.

Mutation/deletion of the adenomatous polyposis coli (APC) tumor suppressor gene in germline cells of rodents and humans is associated with increased intestinal activity of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, and intestinal neoplasia. To study the role of APC in signaling ODC expression, we used the human colon tumor cell line HT29 (wtAPC-/-), which has been stably transfected with a zinc-inducible wild-type APC gene. The addition of ZnCl(2) to HT29-APC cells increased wild-type APC protein and Mad1 RNA and protein and decreased levels of c-myc and ODC RNA and protein, relative to these parameters in HT29 cells transfected with the same plasmid containing the beta-galactosidase gene in place of APC. Upon induction of APC expression, ODC promoter activity and RNA levels were suppressed. When the e-box domain in the 5' flanking region of the ODC gene was mutated, ODC promoter activity was unaffected by wild-type APC expression. Antisense, but not missense, c-myc oligonucleotides decreased ODC activity in HT29 cells expressing mutant APC. These results demonstrated that wild-type APC suppressed c-myc and activated Mad1 expression in HT29 colon-derived cells. These proteins, in turn, regulated the transcription of target genes, including ODC. The data presented indicate that ODC is a modifier of APC-dependent signaling in intestinal cells and tissues.

Base Sequence↗
PubMed1984

Effects of acrylamide and some other sulfhydryl reagents on spontaneous and pathologically induced terminal sprouting from motor end-plates.

The innervation of the normal rat sternocostalis muscle exhibits a constant low level of short spontaneous terminal sprouts visible in zinc iodide-osmium (ZIO) and in methylene blue-stained preparations. Acrylamide inhibits these spontaneous sprouts in a dose-dependent manner. This inhibition is mimicked by N-ethylmaleimide (a sulfhydryl group blocking agent) and can be nullified when acrylamide is given after the sulfhydryl group protecting agent, dithiothreitol (DTT). This could not be reversed by giving DTT 3 hours after acrylamide. Furthermore, when given alone DTT increases the level of spontaneous terminal sprouting seen in ZIO and in methylene blue-stained preparations. These findings suggest that the binding of acrylamide to sulfhydryl groups is involved in the inhibitory process. Acrylamide also reduces the number and length of the reactionary terminal sprouts, seen in ZIO and in methylene blue-stained preparations, that follow partial denervation or local injection of botulinum toxin. These inhibitory effects are long-lasting; recovery still has not fully occurred 4 weeks after a single dose of acrylamide (50 mg/kg). The roles of glutathione and other sulfhydryl components of axons are discussed in relation to the mechanism of acrylamide neurotoxicity.

Acrylamide↗
PubMed2005

Quantitative and immunohistochemical evaluation of PCNA, androgen receptors, apoptosis, and Glutathione-S-Transferase P1 on preneoplastic changes induced by cadmium and zinc chloride in the rat ventral prostate.

BACKGROUND: This study was directed to evaluate the immunoexpression of markers for cell proliferation, apoptosis, nuclear androgen receptors, and Glutathione-S-Transferase P1 (GSTP1), in preneoplastic changes induced by cadmium chloride (Cd) and cadmium plus zinc chloride (Cd + Zn) in rat prostate. METHODS: The following parameters were calculated in ventral prostate of normal rats and rats that received Cd or Cd + Zn in drinking water during 24 months: numerical densities of columnar, basal, and GSTP1 immunoreactive epithelial cells; percentages of cells immunoreactive to: PCNA, (LI(PCNA)), androgen receptors (LI(AR)), and of apoptotic cells. RESULTS: The LI(PCNA) was significantly increased in the animals exposed to Cd + Zn, whereas the numerical densities of both columnar (N(V) columnar cells), and GSTP1 immunoreactive (N(V) GSTP1+) cells were significantly increased in the animals treated with metals in comparison with the controls. No significant differences between the two sources of dysplasias (Cd and Cd + Zn) respecting to LI(PCNA), N(V) columnar cells, and N(V) GSTP1+ were observed. The two types of dysplasias considered together showed a significant increase for the N(V) basal, N(V) columnar, and N(V) GSTP1+ cells in comparison with normal acini of treated and controls. The percentage of apoptotic nuclei did not show significant differences among the three groups studied. CONCLUSIONS: (1) The zinc has little influence in the development of the dysplastic changes of the rat prostate mediated by cadmium. (2) The decrease of apoptosis has little influence in the development of dysplasia. (3) GSTP1 could play a role in the response to the oxidative stress in the dysplastic changes caused by cadmium.

Animals↗
PubMed1989

Immunohistochemical localization of metallothionein in the rat prostate gland during postnatal development.

Immunocytochemical and electrophoretic techniques were used to investigate the presence of metallothionein, a metal-binding protein, in the dorsolateral and ventral lobes of the developing rat prostate. Male rats aged 7 and 14 days were injected subcutaneously with 6 and 20 mg/kg body weight of cadmium and zinc, respectively, or with saline for controls, 24 h prior to tissue sampling. Immunohistochemical localization of metallothionein was observed in the epithelial tissues of the dorsolateral prostate from 7 and 14 day-old animals and in 1 day-old untreated rats. This staining pattern did not appear to be significantly affected by cadmium or zinc treatment. In contrast, metallothionein localization in the ventral prostate decreased with age but demonstrated a slight response to metal-ion treatment in the 7 day-old animals. Electrophoretic and immunoblot analysis confirmed the presence of metallothionein in the control and metal-induced prostate samples from neonatal rats. Lobe-specific differences in localization suggest a functional significance for metallothionein, independent of inducible protein.

Animals↗
PubMed1993

Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II.

The significance of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in the active site of human carbonic anhydrase II has been examined by X-ray crystallographic analyses of site-specific mutants. Mutants with Ala-199 and Ala-106 or Gln-106 have low catalytic activities, while a mutant with Asp-106 has almost full CO2 hydration activity. The structures of these four mutants, as well as that of the bicarbonate complex of the mutant with Ala-199, have been determined at 1.7 to 2.2 A resolution. Removal of the gamma atoms of residue 199 leads to a distorted tetrahedral geometry at the zinc ion, and a catalytically important zinc-bound water molecule has moved towards Glu-106. In the bicarbonate complex of the mutant with Ala-199 one oxygen atom from bicarbonate binds to zinc without displacing this water molecule. Tetrahedral coordination geometries are retained in the mutants at position 106. The mutants with Ala-106 and Gln-106 have a zinc-bound sulfate ion, whereas this sulfate site is only partially occupied in the mutant with Asp-106. The hydrogen-bond network seems to be "reversed" in the mutants with Ala-106 and Gln-106. The network is preserved as in native enzyme in the mutant with Asp-106 but the side chain of Asp-106 is more extended than that of Glu-106 in the native enzyme. These results illustrate the importance of Glu-106 and Thr-199 for controlling the precise coordination geometry of the zinc ion and its ligand preferences which results in an optimal orientation of a zinc-bound hydroxide ion for an attack on the CO2 substrate.

Carbonic Anhydrases↗
PubMed2002

An index technique to monitor broadcast calibration and bait pick up, plus rodent and avian sign under arid conditions.

As part of product-performance and wildlife-hazards studies of 2% zinc phosphide (Zn3P2) steam-rolled-oat baits (11.2 kg ha-1) to reduce vole populations (Microtus spp) in alfalfa (Medicago sativa), we used randomly located, brushed-dirt plots (eight approximately 930-cm2 plots per 0.2-ha enclosure) to monitor bait-broadcast and -removal patterns, as well as to index vole and avian sign. Research was conducted in 18 x 0.2-ha enclosures containing 2.5-year-old stands of alfalfa; a 2-day pre-bait (placebo baits broadcast in all enclosures) period followed by a 14-day test-bait period (placebo and 2% Zn3P2 baits in nine enclosures each) characterized the bait exposures. Baits were broadcast manually by two certified pesticide applicators (CPAs) using Spyker Model-75 spreaders. Baits that fell onto plots were counted < 30 min later to assess the uniformity of bait distribution. The main statistical design was a 2 (placebo or Zn3P2 baits) x 3 (vole-only, vole-pheasant, vole-quail exposures) x 14 (days) factorial, with days considered repeated measurements. In the six vole-only enclosures, baits were removed from the brushed-dirt plots and replaced with four 0% or 2% Zn3P2 baits (one per 232.6-cm2 quadrant; 32 per enclosure); these 'placed' baits were then monitored daily for removal, while the surfaces of all plots were monitored daily for the presence:absence of animal/bird sign. Key results were: (a) 3.51 (+/- 2.66) and 3.39 (+/- 3.52) mean (+/- SD) baits were found on plots after pre-bait and test-bait broadcasts, respectively--less than the predicted 4.52 particles per 930-cm2 plot; (b) baits 'placed' on plots in placebo-baited enclosures were removed earlier than those in Zn3P2-baited enclosures--data in agreement with observed vole mortality; and (c) species x bait interactions occurred for both the vole- and pheasant-sign counts, but not quail-sign counts--data also indirectly confirming Zn3P2-induced mortality effects on voles and pheasants. This technique has utility for a variety of wildlife biology and chemical registration studies; although limited to arid conditions, the technique affords useful indices of broadcast calibration, bait pick-up, as well as target and non-target species mortality.

Animals↗
PubMed2006

Protective effects of Korean herbal remedy against oxidative stress in cardiomyocytes.

Ondamtanggagambang (ODG) has been used as a prescription for psychological anxiety and depression in Korean medicine. In this study, we found that ODG have protective effects against oxidative stress in cardiomyocytes. Pretreatment with ODG extract prevented H2O2 and ZnCl2-induced cell damage in H9c2 cardiomyocytes, whereas simultaneous treatment of ODG extract did not. The protective effect of ODG extract on oxidative stress-induced damage was suppressed significantly by heme oxygenase (HO) inhibitors, zinc protoporphyrin-IX (ZnPP-IX, p < 0.01) and tin protoporphyrin-IX (SnPP-IX, p < 0.01) in H9c2 cells. ODG stimulation of cells strongly induced the expression of HO-1 protein. Taken together, it is suggested that ODG-induced expression of HO-1 may have a beneficial role in cardiomyocytes under oxidative stress.

Animals↗
PubMed2026

A Review on Heat Stress in Broiler Chickens: Mechanisms, Effects and Mitigation Strategies.

BACKGROUND: Heat stress (HS) is a major environmental challenge for broilers, particularly under rising global temperatures and high humidity. Broiler chickens are highly susceptible because of their rapid growth rate, high metabolic heat production, limited thermoregulatory capacity and genetic selection for fast growth. OBJECTIVE: This review aims to synthesise current evidence, evaluate the effectiveness of existing mitigation strategies, identify key knowledge gaps and provide future research directions to improve broiler resilience, welfare and productivity under increasingly HS conditions. METHODS: This review synthesised evidence published between 2010 and 2025 on the physiological, metabolic, intestinal, immunological and productive consequences of HS and evaluated mitigation strategies. RESULTS: The reviewed studies demonstrate that HS reduces feed intake by approximately 10%-30%, suppresses body weight gain and feed efficiency and increases mortality, with severity depending on temperature, humidity and broiler genotype. HS disrupts carbohydrate, protein and lipid metabolism; induces acid-base imbalance and oxidative stress; compromises intestinal barrier integrity; alters gut microbiota; suppresses immune function; and reduces meat quality. Nutritional interventions, including dietary electrolyte balance, antioxidants, vitamins, selenium, zinc, phytogenic compounds, probiotics, betaine and optimised feeding strategies, environmental management and genetic approaches, including naked-neck and frizzle genes, can partially alleviate these adverse effects. However, inconsistencies among studies persist because of differences in broiler strains, environmental conditions, dietary formulations and experimental protocols. CONCLUSION: HS substantially compromises broiler health, welfare, productivity and meat quality. Nutritional, environmental and genetic approaches can partially mitigate its adverse effects; however, further research is needed to improve broiler resilience under increasingly HS conditions.

Animals↗
PubMed1998

Binding of soluble myelin basic protein to various conformational forms of alpha2-macroglobulin.

Myelin basic protein is known to be released into the circulation following traumatic injuries or demyelination within the central nervous system, resulting in the generation of potentially immunogenic myelin basic protein material. In this investigation we have studied the binding of bovine and human myelin basic protein to human alpha2-macroglobulin, which was found to be the only major myelin basic protein-binding protein in human plasma. Myelin basic protein bound to all three conformational forms of alpha2-macroglobulin studied, i.e., native alpha2-macroglobulin, methylamine-treated alpha2-macroglobulin, and chymotrypsin-treated alpha2-macroglobulin. Zinc chloride (1 mM) or 1 mM iodoacetamide partly blocked the complex formation between myelin basic protein and alpha2-macroglobulin, while 1 mM magnesium chloride, 1 mM calcium chloride, or 1 mM EDTA had no effect on binding. Chymotrypsin and trypsin can degrade myelin basic protein to fragments which do not bind to alpha2-macroglobulin. However, when myelin basic protein was complexed with any of the conformational forms of alpha2-macroglobulin, no significant release of Na[125I]-labeled myelin basic protein occurred after proteinase treatment. The results suggest that binding of myelin basic protein to alpha2-macroglobulin may protect extracellular compartments in vivo from immunogenic myelin basic protein fragments and alpha2-macroglobulin may participate in the specific clearance of myelin basic protein from the circulation.

Blood Proteins↗
PubMed2000

One-step purification of rabbit histidine rich glycoprotein by dye-ligand affinity chromatography with metal ion requirement.

A simple method for purification of the histidine rich glycoprotein (rHRG) from rabbit sera was developed. The rHRG was purified by one-step affinity chromatography using the triphenylmethane dye "acid fuchsin" as a specific ligand, which gave an overall yield above 80%. Interestingly, the binding of rHRG to the ligand required the divalent transition-metal ions such as Zn2+, Ni2+, and Co2+ at pH 9.5. In the presence of 0.5 mM ZnCl2, the binding was enhanced 15 times compared with that in the absence of ZnCl2. Bound rHRG was efficiently eluted from the affinity absorbent with 100 mM imidazole or histidine. Purified rHRG was homogeneous with an Mr of 94 kDa when analyzed by SDS-PAGE, whereas isoelectric focusing revealed microheterogeniety with pI values ranging from 6.3 to 6.8. Blotting analysis with lectins specific for carbohydrate moieties and treatment with glycosidases demonstrated that rHRG is a highly N-glycosylated protein with diverse carbohydrate structures.

Animals↗
PubMed2002

Effect of autophosphorylation on the catalytic and regulatory properties of protein tyrosine kinase Src.

The function of autophosphorylation in Src family protein tyrosine kinases is not fully understood. In this paper we compared the catalytic and ligand-binding properties of autophosphorylated and nonautophosphorylated (control) Src. The following are the main differences we found. First, while both forms had the same K(m) for ATP-Mg, autophosphorylated Src had significantly higher K(m) values for the phosphate-accepting substrates, polyE(4)Y, and RCM-lysozyme. The autophosphorylated form also had significantly higher V(max) values than the control. The substrate specificity, as measured by V(max)/K(m) ratio, was altered by autophosphorylation and was dependent on the phosphate-accepting substrate. Second, while autophosphorylation did not affect Src activation by free Mg(2+), Zn(2+), which inhibited Src by competing against an essential Mg(2+) activator, inhibited the control threefold more potently than the autophosphorylated form. Third, autophosphorylation significantly reduced the ability of its SH2 domain to bind phosphotyrosine. Fourth, a Pro-rich Src SH3 domain binding peptide activated the control, but not the autophosphorylated Src even though the apparent binding affinity was not significantly affected by autophosphorylation. These differences indicated that autophosphorylation induced significant and widespread changes in the catalytic and regulatory properties of Src. The implications of these findings relative to Src biological regulation are discussed.

CSK Tyrosine-Protein Kinase↗
PubMed1993

A single protein immunologically identified as CD38 displays NAD+ glycohydrolase, ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities at the outer surface of human erythrocytes.

The three ectoenzyme activities, NAD+ glycohydrolase, ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase were purified to homogeneity from solubilized human erythrocyte membranes. The purification procedure involved three sequential chromatography steps on hydroxylapatite, immobilized Cu++ and immobilized anti-CD38 monoclonal antibody resins. The final step yielded a single 46 kDa protein displaying all three enzymatic activities. Since the protein bound specifically to the anti-CD38 resin, it was immunologically identified as CD38, a 46 kDa surface antigen involved in activation and proliferation of lymphocyte populations.

ADP-ribosyl Cyclase↗
PubMed1995

Differential control of the metal-mediated activation of the human heme oxygenase-1 and metallothionein IIA genes.

Heme oxygenase-1, an essential enzyme in heme catabolism, and metallothionein IIA, a small metal-binding protein with clusters of cysteins, are remarkably induced in HeLa cells following the treatment with cadmium or zinc. Both proteins are considered to be involved in the defense system against metal toxicity. Here we showed by transient expression assays that the cadmium-responsive element (CdRE) of the human heme oxygenase-1 gene is not responsive to zinc, whereas a metal-regulatory element (MRE) of the human metallothionein IIA gene is able to respond to either cadmium or zinc. The CdRE is recognized by a certain nuclear protein(s) which is however unable to bind to an MRE of the metallothionein IIA gene. These results suggest that the metal-selective activation of each gene promoter is mediated by a separate mechanism.

Base Sequence↗