Lipid A-activated inducible nitric oxide synthase expression via nuclear factor-κB in mouse choroid plexus cells.

Choroid plexus (CP) which is responsible for the inflammatory mediators including nitric oxide (NO) are thought to play a crucial role in the process of bacterial meningitis. The present study investigated the mechanisms regulating inducible nitric oxide synthase (iNOS) expression in the choroid plexus epithelium (CPe) in mice. Initially, the expression of iNOS in mouse CPe was strengthened by intracerebroventriclar (i.

Dietary Deficiency of Calcium and/or Iron, an Age-Related Risk Factor for Renal Accumulation of Cadmium in Mice.

The major route of cadmium (Cd) intake by non-smokers is through food ingestion. Cd is a non-essential metal absorbed through one or more transporters of essential metal ions. Expression of these transporters is affected by nutritional status.

Effects of zinc deficiency and supplementation on leptin and leptin receptor expression in pregnant mice.

Leptin is an adipose-derived hormone that primarily regulates energy balance in response to nutrition. Human placental cells produce leptin, whereas murine placental cells produce soluble leptin receptors (Ob-R). However, the roles of these proteins during pregnancy have not been elucidated completely.

Nitric oxide promotes survival of cerebral cortex neurons with simultaneous addition of [Fe(II)(β-citryl-L-glutamate)] complex in primary culture.

It has been reported that the activity of mitochondrial aconitase (m-aconitase) is rapidly inhibited in a variety of cells when exposed to nitric oxide (NO). In present study, we found that NO significantly increased the number of surviving neurons via enhanced mitochondrial functions with simultaneous addition of the [Fe(II)(β-citryl-L-glutamate; β-CG)] complex. In vitro, a variety of aconitase-inhibitors, such as fluorocitrate, cyanide ion, ferricyanide ([Fe(CN)6]), and various oxidants including superoxide anion, inhibited the activity of m-aconitase even in the presence of Fe(II), whereas a NO-donor, nitroprusside (SNP) ([Fe(CN)5NO]), was the only agent that significantly increased activity of that enzyme.

Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation.

Upregulation of Zip14 contributes to hepatic zinc (Zn) and non-transferrin-bound iron (Fe) uptake during infection and inflammation. We investigated whether this essential metal transporter is also involved in hepatic cadmium (Cd) uptake under these conditions. An injection of lipopolysaccharide (LPS), turpentine oil (Tur) and n-hexane (Hex) resulted in an decrease in plasma Zn and Fe concentrations to 25-50% and an increase in hepatic concentrations of both metals to 150-200% of control mice.

Proteomic analysis of the brain tissues from a transgenic mouse model of amyloid β oligomers.

Amyloid β (Aβ) oligomers are presumed to be one of the causes of Alzheimer's disease (AD). Previously, we identified the E693Δ mutation in amyloid precursor protein (APP) in patients with AD who displayed almost no signals of amyloid plaques in amyloid imaging. We generated APP-transgenic mice expressing the E693Δ mutation and found that they possessed abundant Aβ oligomers from 8months of age but no amyloid plaques even at 24months of age, indicating that these mice are a good model to study pathological effects of Aβ oligomers.

Role of megalin and the soluble form of its ligand RAP in Cd-metallothionein endocytosis and Cd-metallothionein-induced nephrotoxicity in vivo.

Orally administered Cd is predominantly distributed to the intestine, and the majority of this mucosal Cd is bound to metallothionein (MT). MT attenuates heavy metal-induced cytotoxicity by sequestering these metals and lowering their intracellular concentrations. In addition, MT acts as an extracellular transporter of orally administered Cd to the kidney.

Oxidation and turnover of renal metallothioneins after an injection of ferric nitrilotriacetate.

Metallothioneins (MTs) have demonstrated strong antioxidant properties, however the biological significance of their effect against hydroxyl radical toxicity remains unclear. We investigated the oxidation and turnover of renal MTs in MT-preinduced mice after an injection of ferric nitrilotriacetate (Fe-NTA). Incubation of MTs with Fe-NTA and H(2)O(2) resulted in a loss of their metal-binding properties and a decrease in their thiol concentration independent of binding potential and isoforms.

β-Citryl-L-glutamate acts as an iron carrier to activate aconitase activity.

The compound β-citryl-L-glutamate (β-CG) was initially isolated from developing brains, though its functional roles remain unclear. In in vitro experiments, the [Fe(II)(β-CG)] complex activated aconitase in the presence of reducing reagents, whereas no Fe complex with citrate, glutamate, or deferoxamine displayed such an effect. β-CG and [Fe(II)(β-CG)] both bound to the fourth labile Fe atom (Fe(a)) in the [4Fe-4S] cluster of aconitase.

Increased hepatic accumulation of ingested Cd is associated with upregulation of several intestinal transporters in mice fed diets deficient in essential metals.

Essential metals (EMs) can affect the metabolism of nonessential metals. It has been suggested that Fe deficiency increases intestinal absorption of Cd via divalent metal transporter 1 (DMT1). To investigate whether EM nutritional status is a host risk factor for Cd accumulation, we studied the effect of nutritional status of Ca, Cu, Mg, Zn, and Fe that most often ingested by humans at levels below recommended dietary allowances on tissue accumulation of orally administered Cd.

Effect of hemolytic and iron-deficiency anemia on intestinal absorption and tissue accumulation of cadmium.

Abnormal iron (Fe) metabolism induces iron-deficiency anemia (FeDA) and also affects body cadmium (Cd) accumulation. However, whether hemolytic anemia also affects Cd metabolism is not known. We compared the intestinal absorption and tissue accumulation of Cd after oral administration of Cd to mice with hemolytic anemia induced by treatment with phenylhydrazine (PHA mice) to that in mice with FeDA.

Involvement of intestinal calcium transporter 1 and metallothionein in cadmium accumulation in the liver and kidney of mice fed a low-calcium diet.

Essential metals can affect the metabolism of nonessential metals. Calcium (Ca) is an essential mineral that is commonly lacking in the diet. When we fed 5-week-old male mice for 4 weeks on a purified diet containing 0.

[Physiological significance of metallothionein in oxidative stress].

Metallothionein (MT), a ubiquitous family of low-molecular weight metal-binding proteins, comprises 30% cysteine residues. Although all of the thiol residues in MT are bound to metals, it still remains active to reactive oxygen species. Each cysteine residue in MT is more effective at protecting DNA from hydroxyl radical attack than the glutathione cysteine in vitro.

Metallothionein-enriched hepatocytes are resistant to ferric nitriloacetate toxicity during conditions of glutathione depletion.

Metallothionein (MT) is involved not only in heavy metal homeostasis/detoxification but also in radical scavenging, yet the relevance to other antioxidant systems and physiological significance under oxidative stress has not been clarified. We studied that ability of MT, induced by zinc and cadmium, to protect against oxidative damage induced by ferric nitrilotriacetate (Fe-NTA) in glutathione depleted primary cell cultures. Treatment with Fe-NTA resulted in significant decreases in cell survival and increases in medium LDH activity in control cells following depletion of glutathione.

Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant.

Metallothionein (MT) demonstrates strong antioxidant properties, yet the physiological relevance of its antioxidant action is not clear. Injection of mice with ferric nitrilotriacetate (Fe-NTA) caused a dose-dependent increase in hepatic and renal MT. Fe-NTA caused a greater increase in hepatic and renal MT concentration (2.

Deciphering the molecular basis of the broad substrate specificity of alpha-glucosidase from Bacillus sp. SAM1606.

The alpha-glucosidase of Bacillus sp. strain SAM1606 is a member of glycosyl hydrolase family 13, and shows an extraordinarily broad substrate specificity and is one of very few alpha-glucosidases that can efficiently hydrolyze the alpha-1,1-glucosidic linkage of alpha,alpha'-trehalose (trehalose). Phylogenetic analysis of family-13 enzymes suggests that SAM1606 alpha-glucosidase may be evolutionally derived from an alpha-1,6-specific ancestor, oligo-1,6-glucosidase (O16G).

Glucocorticoids suppress the inflammation-mediated tolerance to acute toxicity of cadmium in mice.

Several compounds have been shown to cause acute toxicity to cadmium (Cd). The mechanism of tolerance to Cd toxicity induced by glucocorticoids or by inflammation involves induction of metallothionein (MT) synthesis via glucocorticoid response elements or by inflammatory cytokines. We have demonstrated previously that the synthetic glucocorticoid dexamethasone suppresses inflammation-mediated induction of hepatic MT synthesis.