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At least 235 records · Page 13Linked to original sources
PubMed2006

Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells.

An increase in the cytoplasmic-free Ca(2+) concentration mediates cellular responses to environmental signals that influence a range of processes, including gene expression, motility, secretion of hormones and neurotransmitters, changes in energy metabolism, and apoptosis. Mitochondria play important roles in cellular Ca(2+) homeostasis and signaling, but the roles of specific mitochondrial proteins in these processes are unknown. Uncoupling proteins (UCPs) are a family of proteins located in the inner mitochondrial membrane that can dissociate oxidative phosphorylation from respiration, thereby promoting heat production and decreasing oxyradical production. Here we show that UCP4, a neuronal UCP, influences store-operated Ca(2+) entry, a process in which depletion of endoplasmic reticulum Ca(2+) stores triggers Ca(2+) influx through plasma membrane "store-operated" channels. PC12 neural cells expressing human UCP4 exhibit reduced Ca(2+) entry in response to thapsigargin-induced endoplasmic reticulum Ca(2+) store depletion. The elevations of cytoplasmic and intramitochondrial Ca(2+) concentrations and mitochondrial oxidative stress induced by thapsigargin were attenuated in cells expressing UCP4. The stabilization of Ca(2+) homeostasis and preservation of mitochondrial function by UCP4 was correlated with reduced mitochondrial reactive oxygen species generation, oxidative stress, and Gadd153 up-regulation and increased resistance of the cells to death. Reduced Ca(2+)-dependent cytosolic phospholipase A2 activation and oxidative metabolism of arachidonic acid also contributed to the stabilization of mitochondrial function in cells expressing human UCP4. These findings demonstrate that UCP4 can regulate cellular Ca(2+) homeostasis, suggesting that UCPs may play roles in modulating Ca(2+) signaling in physiological and pathological conditions.

Animals↗
PubMed2005

Disruption of iron homeostasis as a mechanism of biologic effect by ambient air pollution particles.

Several features of the clinical presentation and changes in physiology and pathology following exposure to many diverse ambient air pollution particles are comparable, suggesting a common mechanism for their biological effect. We propose that a mechanism of biological effect common to many ambient air pollution particles is a disruption of iron homeostasis in cells and tissues. Among traits shared by every particle-related lung injury is the introduction of a solid-liquid interface into the respiratory tract. All surfaces of particulate matter have some concentration of oxygen-containing functional groups. As a result of its electropositivity, Fe(3+) has a high affinity for oxygen-donor ligands and will react with these groups at the particle surface. Retained particles accumulate metal from available sources in a cell and tissue, and this complexed iron mediates oxidant generation. In addition to complexation onto the solid-liquid interface provided by the surface of particulate matter (PM), there are several alternative pathways by which metal homeostasis in the lower respiratory tract can be disrupted following exposure to ambient air pollution particles to affect an oxidative stress. Evidence suggests that disruption in iron homeostasis following exposures to ambient air pollution particles is an initial event in their biological effect. An association between metal equilibrium in the lower respiratory tract and biological effect in the lung could explain the observed differential toxicity of ultrafine, fine, and coarse particles and disparities in host susceptibility.

Air Pollutants↗
PubMed2004

In silico search for single nucleotide polymorphisms in genes important in vitamin E homeostasis.

Large inter-individual variation exists in the response to vitamin E supplementation, and this may influence the outcome of human studies. It is our hypothesis that genetic heterogeneity is an important determinant of vitamin E homeostasis. Therefore we have performed an in silico search for single nucleotide polymorphisms (SNPs) associated with genes involved in vitamin E homeostasis. Based on function, the following genes were considered as candidates for vitamin E heterogeneity: c-tocopherol transfer protein (TTPA), tocopherol associated protein (TAP), lipoprotein lipase (LPL), multidrug resistance protein 2 (MDR-2), pregnane X receptor (PXR) and members of the cytochrome P450 family (CYP). Searches for coding SNPs were initiated from web based programs of the National Center for Biotechnology Information (NCBI). SNP frequencies were calculated by dividing the number of annotated coding SNPs by the number of base pairs in the open reading frame. Genes for TTPA, TAP and CYP3A5 had calculated SNP frequencies between 503 and 837 base pairs per coding SNP (bp/cSNP) and so are not highly polymorphic. In contrast, cSNP frequencies in LPL, MRP2, PXR, CYP3A4 and CYP4F2 were in the range of 100 bp/cSNP and so are highly polymorphic. Thus proteins involved in specific vitamin E binding are not highly polymorphic, may not influence inter-individual variation and so may not be good candidates for population studies. Proteins involved in drug/lipid metabolism which indirectly influence vitamin E status are highly polymorphic, are likely to influence inter-individual variation and so are good candidates for population studies. We suggest that future studies are aimed at addressing the role of such SNPs in vitamin E homeostasis.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins.

This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B (-/-) mice as well as dramatic alterations in intracellular localization of key components of the Ca(2+) homeostasis machinery in ankyrin-B (-/-) striated muscle and thymus. The sarcoplasmic reticulum (SR) and SR/T-tubule junctions are apparently preserved in a normal distribution in ankyrin-B (-/-) skeletal muscle based on electron microscopy and the presence of a normal pattern of triadin and dihydropyridine receptor. Therefore, the abnormal localization of SR/ER Ca ATPase (SERCA) and ryanodine receptors represents a defect in intracellular sorting of these proteins in skeletal muscle. Extrapolation of these observations suggests defective targeting as the basis for abnormal localization of ryanodine receptors, IP3 receptors and SERCA in heart, and of IP3 receptors in the thymus of ankyrin-B (-/-) mice. Mis-sorting of SERCA 2 and ryanodine receptor 2 in ankyrin-B (-/-) cardiomyocytes is rescued by expression of 220-kD ankyrin-B, demonstrating that lack of the 220-kD ankyrin-B polypeptide is the primary defect in these cells. Ankyrin-B is associated with intracellular vesicles, but is not colocalized with the bulk of SERCA 1 or ryanodine receptor type 1 in skeletal muscle. These data provide the first evidence of a physiological requirement for ankyrin-B in intracellular targeting of the calcium homeostasis machinery of striated muscle and immune system, and moreover, support a catalytic role that does not involve permanent stoichiometric complexes between ankyrin-B and targeted proteins. Ankyrin-B is a member of a family of adapter proteins implicated in restriction of diverse proteins to specialized plasma membrane domains. Similar mechanisms involving ankyrins may be essential for segregation of functionally defined proteins within specialized regions of the plasma membrane and within the Ca(2+) homeostasis compartment of the ER.

Animals↗
PubMed2000

Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor beta II receptor.

The immune system, despite its complexity, is maintained at a relative steady state. Mechanisms involved in maintaining lymphocyte homeostasis are poorly understood; however, recent availability of transgenic (Tg) and knockout mouse models with altered balance of lymphocyte cell populations suggest that cytokines play a major role in maintaining lymphocyte homeostasis. We show here that transforming growth factor (TGF)-beta plays a critical role in maintaining CD8(+) T cell homeostasis in a Tg mouse model that specifically overexpresses a dominant negative TGF-beta II receptor (DNRII) on T cells. DNRII T cell Tg mice develop a CD8(+) T cell lymphoproliferative disorder resulting in the massive expansion of the lymphoid organs. These CD8(+) T cells are phenotypically "naive" except for the upregulation of the cell surface molecule CD44, a molecule usually associated with memory T cells. Despite their dominance in the peripheral lymphoid organs, CD8(+) T cells appear to develop normally in the thymus, suggesting that TGF-beta exerts its homeostatic control in the peripheral immune system.

Animals↗
PubMed2000

Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells.

The developmental requirements for immunological memory, a central feature of adaptive immune responses, is largely obscure. We show that as naive CD8 T cells undergo homeostasis-driven proliferation in lymphopenic mice in the absence of overt antigenic stimulation, they progressively acquire phenotypic and functional characteristics of antigen-induced memory CD8 T cells. Thus, the homeostasis-induced memory CD8 T cells express typical memory cell markers, lyse target cells directly in vitro and in vivo, respond to lower doses of antigen than naive cells, and secrete interferon gamma faster upon restimulation. Like antigen-induced memory T cell differentiation, the homeostasis-driven process requires T cell proliferation and, initially, the presence of appropriate restricting major histocompatibility complexes, but it differs by occurring without effector cell formation and without requiring interleukin 2 or costimulation via CD28. These findings define repetitive cell division plus T cell receptor ligation as the basic requirements for naive to memory T cell differentiation.

Adoptive Transfer↗
PubMed1998

Traumatic brain injury alters synaptic homeostasis: implications for impaired mitochondrial and transport function.

This study utilized a unilateral controlled cortical impact model of traumatic brain injury to assess disruptions of synaptic homeostasis following trauma. Adult rats were subjected to a moderate (2 mm) cortical deformation and synaptosomes were prepared from the entire ipsilateral (injured) hemisphere or dissected into different regions (hippocampus, injured cortical area including penumbra, residual hemisphere) at various times postinjury (10 and 30 min, and 1, 6, and 24 h). Synaptosomes from the corresponding regions of the contralateral hemisphere were used as controls to assess alterations in synaptic ATP levels, lipid peroxidation, and glutamate and glucose transport. The results demonstrate significant time-dependent alterations in synaptic homeostasis, which included an immediate reduction in ATP levels, coupled with a significant increase in lipid peroxidation within 30 min postinjury. Lipid peroxidation demonstrated a biphasic response with elevations observed 24 h postinjury, a time at which decreases in glutamate and glucose transport occurred. These results suggest that disruption of synaptic homeostasis is an extremely early event following trauma that should be considered when designing pharmacological interventions.

Adenosine Triphosphate↗
PubMed2005

Peripheral metabolism of thyroid hormone and glucose homeostasis.

Thyroid hormone action has long been recognized as an important determinant of glucose homeostasis. Recent advances in the knowledge of the physiology of the deiodinases indicate that through tissue-specific regulation of thyroid hormone metabolism, leading to local specificity of thyroid hormone action and target gene transcription patterns, they may have an important function in the modulation of carbohydrate metabolism. This review briefly addresses the role of thyroid hormone action on glucose homeostasis with a specific focus on the significance of the peripheral metabolism of thyroid hormone in the regulation of glucose homeostasis and insulin sensitivity.

Alleles↗
PubMed2002

Two distinctly localized p-type ATPases collaborate to maintain organelle homeostasis required for glycoprotein processing and quality control.

Membrane transporter proteins are essential for the maintenance of cellular ion homeostasis. In the secretory pathway, the P-type ATPase family of transporters is found in every compartment and the plasma membrane. Here, we report the identification of COD1/SPF1 (control of HMG-CoA reductase degradation/SPF1) through genetic strategies intended to uncover genes involved in protein maturation and endoplasmic reticulum (ER)-associated degradation (ERAD), a quality control pathway that rids misfolded proteins. Cod1p is a putative ER P-type ATPase whose expression is regulated by the unfolded protein response, a stress-inducible pathway used to monitor and maintain ER homeostasis. COD1 mutants activate the unfolded protein response and are defective in a variety of functions apart from ERAD, which further support a homeostatic role. COD1 mutants display phenotypes similar to strains lacking Pmr1p, a Ca(2+)/Mn(2+) pump that resides in the medial-Golgi. Because of its localization, the previously reported role of PMR1 in ERAD was somewhat enigmatic. A clue to their respective roles came from observations that the two genes are not generally required for ERAD. We show that the specificity is rooted in a requirement for both genes in protein-linked oligosaccharide trimming, a requisite ER modification in the degradation of some misfolded glycoproteins. Furthermore, Cod1p, like Pmr1p, is also needed for the outer chain modification of carbohydrates in the Golgi apparatus despite its ER localization. In strains deleted of both genes, these activities are nearly abolished. The presence of either protein alone, however, can support partial function for both compartments. Taken together, our results reveal an interdependent relationship between two P-type ATPases to maintain homeostasis of the organelles where they reside.

ATP-Binding Cassette Transporters↗
PubMed2004

Genetic and environmental factors influencing glutathione homeostasis in Saccharomyces cerevisiae.

Glutathione is an essential metabolite protecting cells against oxidative stress and aging. Here, we show that endogenously synthesized glutathione undergoes intercellular cycling during growth to stationary phase. Genome-wide screening identified approximately 270 yeast deletion mutants that overexcrete glutathione, predominantly in the reduced form, and identified a surprising set of functions important for glutathione homeostasis. The highest excretors were affected in late endosome/vacuolar functions. Other functions identified included nitrogen/carbon source signaling, mitochondrial electron transport, ubiquitin/proteasomal processes, transcriptional regulation, ion transport and the cellular integrity pathway. For many mutants the availability of branched chain amino acids and extracellular pH influenced both glutathione homeostasis and cell viability. For all mutants tested, the onset of glutathione excretion occurred when intracellular concentration exceeded the maximal level found in the parental strain; however, in some mutants prolonged excretion led to substantial depletion of intracellular glutathione. These results significantly contribute to understanding mechanisms affecting glutathione homeostasis in eukaryotes and may provide insight into the underlying cause of glutathione depletion in degenerative processes such as Parkinson's disease. The important implications of these data for use of the yeast deletion collection for the study of other phenomena also are discussed.

Amino Acids↗
PubMed2002

Zinc homeostasis during lactation in a population with a low zinc intake.

BACKGROUND: There is a major increase in endogenous zinc excretion, specifically via the mammary gland, in early human lactation. Whereas fractional absorption of dietary zinc has been reported to increase in early human lactation, it is not known to what extent adaptive mechanisms may maintain zinc homeostasis, especially when dietary zinc intake is relatively low. OBJECTIVE: The objective of this study was to quantitate major variables of zinc homeostasis during early lactation in subjects from a population whose habitual dietary zinc intake is low. DESIGN: We studied 18 free-living lactating women from a rural community of northeast China whose infants were exclusively breast-fed. The subjects were studied at approximately 2 mo of lactation with use of stable isotopes of zinc and metabolic collection techniques. Milk volume was measured with use of a deuterium enrichment method. RESULTS: The mean (+/-SD) secretion of zinc in milk was 2.01 +/- 0.97 mg/d, the intake of zinc was 7.64 +/- 1.61 mg/d, and the fractional absorption of zinc was 0.53 +/- 0.09, for a total daily zinc absorption of 4.00 +/- 0.71 mg/d. Endogenous zinc excretion in urine and feces was 0.30 +/- 0.10 and 1.66 +/- 0.97 mg/d, respectively. CONCLUSIONS: Zinc balance, including zinc secreted in breast milk, was maintained at approximately 2 mo of lactation in women whose habitual diet was low in zinc. Homeostasis was achieved by high fractional absorption of zinc and intestinal conservation of endogenous fecal zinc.

Adult↗
PubMed1999

Mitochondrial intermediate peptidase and the yeast frataxin homolog together maintain mitochondrial iron homeostasis in Saccharomyces cerevisiae.

Friedreich's ataxia (FRDA) is a neurodegenerative disease typically caused by a deficiency of frataxin, a mitochondrial protein of unknown function. In Saccharomyces cerevisiae, lack of the yeast frataxin homolog ( YFH1 gene, Yfh1p polypeptide) results in mitochondrial iron accumulation, suggesting that frataxin is required for mitochondrial iron homeostasis and that FRDA results from oxidative damage secondary to mitochondrial iron overload. This hypothesis implies that the effects of frataxin deficiency could be influenced by other proteins involved in mitochondrial iron usage. We show that Yfh1p interacts functionally with yeast mitochondrial intermediate peptidase ( OCT1 gene, YMIP polypeptide), a metalloprotease required for maturation of ferrochelatase and other iron-utilizing proteins. YMIP is activated by ferrous iron in vitro and loss of YMIP activity leads to mitochondrial iron depletion, suggesting that YMIP is part of a feedback loop in which iron stimulates maturation of YMIP substrates and this in turn promotes mitochondrial iron uptake. Accordingly, YMIP is active and promotes mitochondrial iron accumulation in a mutant lacking Yfh1p ( yfh1 [Delta]), while genetic inactivation of YMIP in this mutant ( yfh1 [Delta] oct1 [Delta]) leads to a 2-fold reduction in mitochondrial iron levels. Moreover, overexpression of Yfh1p restores mitochondrial iron homeostasis and YMIP activity in a conditional oct1 ts mutant, but does not affect iron levels in a mutant completely lacking YMIP ( oct1 [Delta]). Thus, we propose that Yfh1p maintains mitochondrial iron homeostasis both directly, by promoting iron export, and indirectly, by regulating iron levels and therefore YMIP activity, which promotes mitochondrial iron uptake. This suggests that human MIP may contribute to the functional effects of frataxin deficiency and the clinical manifestations of FRDA.

Animals↗
PubMed2000

Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae.

Frataxin is a nuclear-encoded mitochondrial protein widely conserved among eukaryotes. Human frataxin (fxn) is severely reduced in Friedreich ataxia (FRDA), a frequent autosomal recessive neuro- and cardio-degenerative disease. Whereas the function of fxn is unknown, the yeast frataxin homolog (Yfh1p) has been shown to be involved in mitochondrial iron homeostasis and protection from free radical toxicity. Evidence of iron accumulation and oxidative damage in cardiac tissue from FRDA patients suggests that fxn may have a similar function, but whether yeast and human frataxin actually have interchangeable roles in mitochondrial iron homeostasis is unknown. We show that a wild-type FRDA cDNA can complement Yfh1p-deficient yeast (yfh1 delta) by preventing the mitochondrial iron accumulation and oxidative damage associated with loss of Yfh1p. We analyze the functional effects of two FRDA point mutations, G130V and W173G, associated with a mild and a severe clinical presentation, respectively. The G130V mutation affects protein stability and results in low levels of mature (m) fxn, which are nevertheless sufficient to rescue yfh1 delta yeast. The W173G mutation affects protein processing and stability and results in severe m-fxn deficiency. Expression of the FRDA (W173G) cDNA in yfh1 delta yeast leads to increased levels of mitochondrial iron which are not as elevated as in Yfh1p-deficient cells but are above the threshold for oxidative damage of mitochondrial DNA and iron-sulfur centers, causing a typical yfh1 delta phenotype. These results demonstrate that fxn functions like Yfh1p, providing experimental support to the hypothesis that FRDA is a disorder of mitochondrial iron homeostasis.

Cell Line↗
PubMed1983

Long-term effects of excess protein and phosphorus on bone homeostasis in adult mice.

In adult human subjects, an interaction between dietary protein and phosphorus has been reported, in which the hypercalciuric effect of excess protein is counteracted by the hypocalciuric effect of phosphorus, with restoration of calcium balance. In adult rodents, bone homeostasis is maintained over a wide range of protein intakes, whereas high phosphorus diets cause bone loss, despite their hypocalciuric effect, as the result of an overriding increase in the excretion of endogenous fecal calcium. The present study was designed to determine whether there is an interaction between dietary protein and phosphorus with respect to bone homeostasis in adult mice. Four-month-old 45Ca-labeled B6D2F1 female mice were fed for 52 weeks the following diets (in percent): control, Ca, 0.6; P, 0.3; protein, 15; high P, Ca. 0.6; P, 1.2; protein, 15; high protein, Ca, 0.6; P, 0.3; protein, 30; and high P + high protein, Ca, 0.6; P, 1.2; protein, 30. Urinary calcium was persistently increased in the high protein group, depressed in the high P group and transiently depressed in the high P + high protein group. Excess dietary protein prevented phosphorus-induced kidney calcinosis. 45Ca loss was increased in the high P groups, but not in the high protein group. There were significant decreases in the mass of the femurs and tibias in both high P groups, whereas there was no effect of high protein intake. These results show that bone homeostasis in adult mice is sensitive to excess dietary phosphorus but not to excess protein, and that there is no interaction between these nutrients with respect to their effects on bone.

Animals↗
PubMed1988

Effect of dietary retinoic acid on circulatory vitamin A homeostasis in polybrominated biphenyl-treated rats.

Retinoic acid (RA) supplementation is known to lower the amount of retinol in circulation. In contrast, the feeding of polyhalogenated aromatic hydrocarbons results in an elevated level of circulatory retinol. We investigated the effect of short-term dietary exposure to RA on the amount of serum retinol in female Sprague-Dawley rats fed either a basal diet (control rats) or the basal diet containing 100 mg of polybrominated biphenyls (PBBs)/kg diet (PBB-treated rats). After feeding of the above diets for 137 d, RA (12 mg/kg diet) was included in both the control and PBB-containing diets. The rats were fed the RA-containing diet for 3 d and then killed (d 140). Blood samples were obtained before and after RA treatment. Chronic PBB treatment of rats resulted in lower hepatic vitamin A and higher kidney vitamin A than in control rats. Serum retinol concentration was significantly higher in rats treated with PBB for 137 d than in controls; the subsequent treatment with RA lowered serum retinol to a level that was not different from that of control rats treated with RA. Our observations agree with earlier findings that 1) PBB treatment alters vitamin A homeostasis, and 2) dietary RA lowers the amount of circulatory retinol. An important new observation is that serum retinol homeostasis in PBB-treated rats appears to be regulated by a mechanism similar to that of normal rats. Polyhalogenated aromatic hydrocarbons may thus be useful tools to study the control mechanisms of vitamin A homeostasis.

Animals↗
PubMed2004

Energy homeostasis, obesity and eating disorders: recent advances in endocrinology.

Health problems resulting from obesity could offset many of the recent health gains achieved by modern medicine, and obesity may replace tobacco as the number one health risk for developed societies. An estimated 300,000 deaths per year and significant morbidity are directly attributable to obesity, mainly due to heart disease, diabetes, cancer, asthma, sleep apnea, arthritis, reproductive complications and psychological disturbances. In parallel with the increasing prevalence of obesity, there has been a dramatic increase in the number of scientific and clinical studies on the control of energy homeostasis and the pathogenesis of obesity to further our understanding of energy balance. It is now recognized that there are many central and peripheral factors involved in energy homeostasis, and it is expected that the understanding of these mechanisms should lead to effective treatments for the control of obesity. This brief review discusses the potential role of several recently discovered molecular pathways involved in the control of energy homeostasis, obesity and eating disorders.

Adiponectin↗
PubMed2006

Alkali cation exchangers: roles in cellular homeostasis and stress tolerance.

Uptake and translocation of cations play essential roles in plant nutrition, signal transduction, growth, and development. Among them, potassium (K+) and sodium (Na+) have been the focus of numerous physiological studies because K+ is an essential macronutrient and the most abundant inorganic cation in plant cells, whereas Na+ toxicity is a principal component of the deleterious effects associated with salinity stress. Although the homeostasis of these two ions was long surmised to be fine tuned and under complex regulation, the myriad of candidate membrane transporters mediating their uptake, intracellular distribution, and long-distance transport is nevertheless perplexing. Recent advances have shown that, in addition to their function in vacuolar accumulation of Na+, proteins of the NHX family are endosomal transporters that also play critical roles in K+ homeostasis, luminal pH control, and vesicle trafficking. The plasma membrane SOS1 protein from Arabidopsis thaliana, a highly specific Na+/H+ exchanger that catalyses Na+ efflux and that regulates its root/shoot distribution, has also revealed surprising interactions with K+ uptake mechanisms by roots. Finally, the function of individual members of the large CHX family remains largely unknown but two CHX isoforms, AtCHX17 and AtCH23, have been shown to affect K+ homeostasis and the control of chloroplast pH, respectively. Recent advances on the understanding of the physiological processes that are governed by these three families of cation exchangers are reviewed and discussed.

Arabidopsis Proteins↗
PubMed2006

Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis.

Nicotine reduces beta-amyloidosis and has a beneficial effect against Alzheimer's disease (AD), but the underlying mechanism is not clear. The abnormal interactions of beta-amyloid (Abeta) with metal ions such as copper and zinc are implicated in the process of Abeta deposition in AD brains. In the present study, we investigated the effect of nicotine on metal homeostasis in the hippocampus and cortex of APP(V717I) (London mutant form of APP) transgenic mice. A significant reduction in the metal contents of copper and zinc in senile plaques and neuropil is observed after nicotine treatment. The densities of copper and zinc distributions in a subfield of the hippocampus CA1 region are also reduced after nicotine treatment. We further studied the mechanism of nicotine-mediated effect on metal homeostasis by using SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw). Nicotine treatment decreases the intracellular copper concentration and attenuates Abeta-mediated neurotoxicity facilitated by the addition of copper, and these effects are independent of the activation of nicotinic acetylcholine-receptor. These data suggest that the effect of nicotine on reducing beta-amyloidosis is partly mediated by regulating metal homeostasis.

Amyloid beta-Peptides↗