Nickel toxicity in plants: reasons, toxic effects, tolerance mechanisms, and remediation possibilities-a review.

Nickel (Ni) is a naturally occurring metal, but anthropogenic activities such as industrialization, use of fertilizers, chemicals, and sewage sludge have increased its concentration in the environment up to undesirable levels. Ni is considered to be essential for plant growth at low concentration; however, Ni pollution is increasing in the environment, and therefore, it is important to understand its functional roles and toxic effects on plants. This review emphasizes the environmental sources of Ni, its essentiality, effects, tolerance mechanisms, possible remediation approaches, and research direction that may help in interdisciplinary studies to assess the significance of Ni toxicity. Briefly, Ni affects plant growth both positively and negatively, depending on the concentration present in the growth medium. On the positive side, Ni is essential for normal growth, enzymatic activities (e.g., urease), nitrogen metabolism, iron uptake, and specific metabolic reactions. On the negative side, Ni reduces seed germination, root and shoot growth, biomass accumulation, and final production. Moreover, Ni toxicity also causes chlorosis and necrosis and inhibits various physiological processes (photosynthesis, transpiration) and cause oxidative damage in plants. The threat associated with Ni is increased as Ni concentration increases day by day in the environment, particularly in soils; therefore, it would be hazardous for crop production in the near future. Additionally, the lack of information regarding the mechanisms of Ni tolerance in plants further intensifies this situation. Therefore, future research should be focused on approachable and prominent solutions in order to minimize the entry of Ni into our ecosystems.

[Nickel - role in human organism and toxic effects]. / Nikiel - rola w organizmie czlowieka i dzialanie toksyczne.

The aim of this study is to familiarize the Role of nickel in the Environment and in living organisms. This metal is widely used in many fields such as electrical engineering, medicine, Jewellery or Automotive Industry. Furthermore, it's an important part of our food. As the central atom of bacterial enzymes it participates in degradation of urea.. Nickel is also an micronutritient essential for proper functioning of the human body, as it increases hormonal activity and is involved in lipid metabolism. This metal makes it's way to the human body through respiratory tract, digestive system and skin. Large doses of nickel or prolonged contact with it could cause a variety of side effects. Harmfull effects of Nickel are genotoxicity haematotoxicity, teratogenicity, immunotoxicity and carcinogenicity. The population of people allergic to nickel is growing, it occcurs much more often to the women and it can appear in many way. Hypersensitivity to nickel can also be occupational. Due to the increasing prevalence of allergies to nickel. European regulations have been introduced to reduce the content of this metal in products of everyday usage. In countries which have fulfilled the above-mentioned law, the plunge of hypersensitivities has been observed.

Nickel superoxide dismutase: structural and functional roles of His1 and its H-bonding network.

Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the presence of a H-bonding network formed between the NH group of the apical imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit in the hexameric enzyme. This interaction is supported by another intrasubunit H-bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were produced to experimentally evaluate the roles of this H-bonding network and compare the results with prior predictions from density functional theory calculations. The X-ray crystal structure of H1A-NiSOD, which lacks the apical ligand entirely, reveals that in the absence of the Glu17-His1 H-bond, the active site is disordered. Characterization of this variant using X-ray absorption spectroscopy (XAS) shows that Ni(II) is bound in the expected N2S2 planar coordination site. Despite these structural perturbations, the H1A-NiSOD variant retains 4% of wild-type (WT) NiSOD activity. Three other mutations were designed to preserve the apical imidazole ligand but perturb the H-bonding network: R47A-NiSOD, which lacks the intramolecular H-bonding interaction; E17R/R47A-NiSOD, which retains the intramolecular H-bond but lacks the intermolecular Glu17-His1 H-bond; and E17A/R47A-NiSOD, which lacks both H-bonding interactions. These variants were characterized by a combination of techniques, including XAS to probe the nickel site structure, kinetic studies employing pulse-radiolytic production of superoxide, and electron paramagnetic resonance to assess the Ni redox activity. The results indicate that in addition to the roles in redox tuning suggested on the basis of previous computational studies, the Glu17-His1 H-bond plays an important structural role in the proper folding of the "Ni-hook" motif that is a critical feature of the active site.

Structure of the nucleotide-binding domain of a dipeptide ABC transporter reveals a novel iron-sulfur cluster-binding domain.

Dipeptide permease (Dpp), which belongs to an ABC transport system, imports peptides consisting of two or three L-amino acids from the matrix to the cytoplasm in microbes. Previous studies have indicated that haem competes with dipeptides to bind DppA in vitro and in vivo and that the Dpp system can also translocate haem. Here, the crystal structure of DppD, the nucleotide-binding domain (NBD) of the ABC-type dipeptide/oligopeptide/nickel-transport system from Thermoanaerobacter tengcongensis, bound with ATP, Mg(2+) and a [4Fe-4S] iron-sulfur cluster is reported. The N-terminal domain of DppD shares a similar structural fold with the NBDs of other ABC transporters. Interestingly, the C-terminal domain of DppD contains a [4Fe-4S] cluster. The UV-visible absorbance spectrum of DppD was consistent with the presence of a [4Fe-4S] cluster. A search with DALI revealed that the [4Fe-4S] cluster-binding domain is a novel structural fold. Structural analysis and comparisons with other ABC transporters revealed that this iron-sulfur cluster may act as a mediator in substrate (dipeptide or haem) binding by electron transfer and may regulate the transport process in Dpp ABC transport systems. The crystal structure provides a basis for understanding the properties of ABC transporters and will be helpful in investigating the functions of NBDs in the regulation of ABC transporter activity.

Metals essentials for plants: the nickel case.

The long period of research that preceded the discovery of nickel (Ni) essentiality for plants constitutes a paradigmatic case of doubts and uncertainties that often occur in experimental biology. The history of the essentiality of chemical elements that are present as traces in the plant ash (micronutrients) began in the mid-Nineteenth, but it had blurred outlines until Daniel Arnon, towards the mid-twentieth century, fixed the now historic 'criteria of essentiality'. During this rather long time, seven micronutrients were recognised, step by step, as essential for higher plants, (iron, manganese, boron, Zinc, copper, molybdenum, and chloride), at first thanks to meticulous observations of deficiency symptoms and then to the culture of plant on aqueous solutions. The last element to be recognised as essential for plant nutrition was Ni, which was considered a very toxic element for more than a century. Towards the Thirties, Ni became to be regarded as a useful element by some researchers, but the ultimate proof of its essentiality was obtained only in the Eighties, when the American group of Ross M. Welch demonstrated that Ni is a cofactor of the enzyme urease. More recent research shows that Ni improves the nitrogen (N) metabolism and appears to be important for the efficiency of N fixation.

Nickel differentially regulates NFAT and NF-κB activation in T cell signaling.

Nickel is a potent hapten that induces contact hypersensitivity in human skin. While nickel induces the maturation of dendritic cells via NF-κB and p38 MAPK activation, it also exerts immunosuppressive effects on T cells through an unknown mechanism. To elucidate the molecular mechanisms of its effects on T cells, we examined the effects of NiCl(2) on mRNA expression in human CD3+ T cells stimulated with CD3 and CD28 antibodies. Using a DNA microarray and Gene Ontology, we identified 70 up-regulated (including IL-1ß, IL-6 and IL-8) and 61 down-regulated (including IL-2, IL-4, IL-10 and IFN-γ) immune responsive genes in NiCl(2)-treated T cells. The DNA microarray results were verified using real-time PCR and a Bio-Plex(TM) suspension protein array. Suppression of IL-2 and IFN-γ gene transcription by NiCl(2) was also confirmed using Jurkat T cells transfected with IL-2 or IFN-γ luciferase reporter genes. To explore the NiCl(2)-regulated signaling pathway, we examined the binding activity of nuclear proteins to NFAT, AP-1, and NF-κB consensus sequences. NiCl(2) significantly and dose-dependently suppressed NFAT- and AP-1-binding activity, but augmented NF-κB-binding activity. Moreover, NiCl(2) decreased nuclear NFAT expression in stimulated T cells. Using Jurkat T cells stimulated with PMA/ionomycin, we demonstrated that NiCl(2) significantly suppressed stimulation-evoked cytosolic Ca(2+) increases, suggesting that NiCl(2) regulates NFAT signals by acting as a blocker of Ca(2+) release-activated Ca(2+) (CRAC) channels. These data showed that NiCl(2) decreases NFAT and increases NF-κB signaling in T cells. These results shed light on the effects of nickel on the molecular regulation of T cell signaling.

Resorte de Coffin: estudio de 2 diferentes tipos de ligas metálicas / Coffin appliance: study of 2 different types of metal alloys

La aparición de los alambres con una baja cantidad de níquel son un gran avance en ortodoncia, supliendo la necesidad de ortodoncia para pacientes que pueden tener hipersensibilidad de este ión, pero no se conoce mucho acerca de las propiedades mecánicas de estos alambres. El objetivo de este estudio fue probar la hipótesis de que no hay diferencia en el desempeño mecánico de los alambres de acero inoxidable y alambres de acero inoxidable con bajo contenido de níquel, evaluando la fuerza, resistencia y módulo de elasticidad producida por el resorte de Coffin hecho con alambre de 0,032 y 0,036 pulgadas. Se construyeron 60 unidades de Coffin, 30 para cada tipo de aleación, siendo 15confeccionadas con alambre de 0,032 pulgadas y 15 con alambre de 0,036 pulgadas. Todos los arcos fueron sometidos a la prueba mecánica de compresión en la máquina EMIC DL-10000, simulando 4, 6, 9 y 12 mm de activación. El análisis de varianza y comparación múltiple (ANOVA) y la prueba de Tukey (p <0,05) fueron utilizados para evaluar la fuerza, resistencia y módulo de elasticidad. Los grupos que utilizaron alambre de 0,036 pulgadas presentaron estadísticamente (p <0,05) mayores niveles de fuerza, resistencia y módulo de elasticidad en comparación con dispositivos con 0,032 pulgadas de alambre para ambas aleaciones. Para el mismo espesor, no hubieron diferencias estadísticamente significativas entre los 2 tipos de aleaciones, con excepción de los dispositivos con activación de 9 mm y espesor de 0,036 pulgadas que mostraron una diferencia estadística (p <0,05). Los resortes de Coffin evaluados para ambas aleaciones metálicas produjeron fuerzas adecuadas para el tratamiento ortodontico, por lo que debe ser correctamente planificada su aplicación clínica.

The emergence of stainless steel wire made of low-nickel content was a major breakthrough in the orthodontic, supplying the need for orthodontics patients who may have hypersensitivity by this ion, but do not know much about the mechanical properties of these wires. The objective of this study is to test the hypothesis that there is no difference between stainless steel wires and low-nickel stainless steel ones regarding their mechanical behaviour. Force, resilience, and elasticity modulus produced by Coffin appliances made of 0.032-inch and 0.036-inch wires were evaluated. Sixty appliances Coffin were made, thirty for each type of alloy being fifteen for each wire thickness. All the arches were submitted to mechanical compression test by using an EMIC DL-10000 machine simulating activations of 4, 6, 9, and 12 mm. Analysis of variance (ANOVA) with multiple comparisons and Tukey’s test were employed (p< 0.05) for assessing force, resilience, and elasticity modulus. The groups using the 0.036 inch presented statistically (p<0.05) higher levels of force, resiliency and elasticity modulus when compared to the arches using the 0.032 inch wire for both alloys. The Coffin appliances for both alloys evaluated can produce adequate forces for orthodontic treatment as long as their clinical application is correctly planned.

Nickel-based Enzyme Systems.

Of the eight known nickel enzymes, all but glyoxylase I catalyze the use and/or production of gases central to the global carbon, nitrogen, and oxygen cycles. Nickel appears to have been selected for its plasticity in coordination and redox chemistry and is able to cycle through three redox states (1+, 2+, 3+) and to catalyze reactions spanning approximately 1.5 V. This minireview focuses on the catalytic mechanisms of nickel enzymes, with an emphasis on the role(s) of the metal center. The metal centers vary from mononuclear to complex metal clusters and catalyze simple hydrolytic to multistep redox reactions.

Role of conserved tyrosine residues in NiSOD catalysis: a case of convergent evolution.

Superoxide dismutases rely on protein structural elements to adjust the redox potential of the metallocenter to an optimum value near 300 mV (vs NHE), to provide a source of protons for catalysis, and to control the access of anions to the active site. These aspects of the catalytic mechanism are examined herein for recombinant preparations of the nickel-dependent SOD (NiSOD) from Streptomyces coelicolor and for a series of mutants that affect a key tyrosine residue, Tyr9 (Y9F-, Y62F-, Y9F/Y62F-, and D3A-NiSOD). Structural aspects of the nickel sites are examined by a combination of EPR and X-ray absorption spectroscopies, and by single-crystal X-ray diffraction at approximately 1.9 A resolution in the case of Y9F- and D3A-NiSODs. The functional effects of the mutations are examined by kinetic studies employing pulse radiolytic generation of O2- and by redox titrations. These studies reveal that although the structure of the nickel center in NiSOD is unique, the ligand environment is designed to optimize the redox potential at 290 mV and results in the oxidation of 50% of the nickel centers in the oxidized hexamer. Kinetic investigations show that all of the mutant proteins have considerable activity. In the case of Y9F-NiSOD, the enzyme exhibits saturation behavior that is not observed in wild-type (WT) NiSOD and suggests that release of peroxide is inhibited. The crystal structure of Y9F-NiSOD reveals an anion binding site that is occupied by either Cl- or Br- and is located close to but not within bonding distance of the nickel center. The structure of D3A-NiSOD reveals that in addition to affecting the interaction between subunits, this mutation repositions Tyr9 and leads to altered chemistry with peroxide. Comparisons with Mn(SOD) and Fe(SOD) reveal that although different strategies for adjusting the redox potential and supply of protons are employed, NiSOD has evolved a similar strategy for controlling the access of anions to the active site.

Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones.

The neurodegenerative disorder Friedreich's ataxia (FRDA) is caused by mutations in frataxin, a mitochondrial protein whose function remains controversial. Using co-immunoprecipitation and mass spectrometry we identified multiple interactors of mitochondrial frataxin in mammalian cells. One interactor was mortalin/GRP75, a homolog of the yeast ssq1 chaperone that integrates iron-sulfur clusters into imported mitochondrial proteins. Another interactor was ISD11, recently identified as a component of the eukaryotic complex Nfs1/ISCU, an essential component of iron-sulfur cluster biogenesis. Interactions between frataxin and ISD11, and frataxin and GRP75 were confirmed by co-immunoprecipitation experiments in both directions. Immunofluorescence analysis demonstrated that ISD11 co-localized with both frataxin and with mitochondria. The point mutations I154F and W155R in frataxin cause FRDA and are clustered to one surface of the protein, and these mutations decrease the interaction of frataxin with ISD11. The frataxin/ISD11 interaction was also decreased by the chelator EDTA, and was increased by supplementation with nickel but not other metal ions. Nickel supplementation rescued the defective interaction of mutant frataxin I154F and W155R with ISD11. Upon ISD11 depletion by siRNA in HEK293T cells, the amount of the Nfs1/ISCU protein complex declined, as did the activity of the iron-sulfur cluster enzyme aconitase, while the cellular iron content was increased, as seen in tissues from FRDA patients. Furthermore, ISD11 mRNA levels were decreased in FRDA patient cells. These data suggest that frataxin binds the iron-sulfur biogenesis Nfs1/ISCU complex through ISD11, that the interaction is nickel-dependent, and that multiple consequences of frataxin deficiency are duplicated by ISD11 deficiency.

The RcnRA (YohLM) system of Escherichia coli: a connection between nickel, cobalt and iron homeostasis.

The transporter RcnA has previously been implicated in Ni(II) and Co(II) detoxification in E. coli probably through efflux. Here we demonstrate that the divergently described rcnA and rcnR gene products constitute a link between nickel, cobalt and iron homeostasis. Deletion of the rcnA gene resulted in increased cellular nickel, cobalt and iron concentrations. Expression of rcnA was induced by Ni(II) or Co(II). Overproduction of rcnR inhibited induction of rcnA by metal cations but RcnR did not bind to the rcnA promoter in vitro. When rcnR or fur, the gene of the global repressor of iron homeostasis, was deleted, expression of rcnA was also induced by iron. The promoter region of rcnA was positive in a Fur titration (FURTA) in vivo assay indicative of Fur binding. Thus, rcnA is part of the Fur regulon of E. coli. The implications of a connection between the homoeostasis of closely related transition metals are discussed.

The role of Ni(2+)-sensitive T-type Ca(2+) channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder.

OBJECTIVE: To explore the role of Ni(2+)-sensitive T-type Ca(2+) channels in the generation of spontaneous excitation of detrusor smooth muscles. MATERIALS AND METHODS: In isolated detrusor smooth muscle bundles of the guinea-pig bladder, changes in the membrane potential and muscle tension were measured using intracellular microelectrodes and isometric tension recording. Changes in the intracellular Ca(2+) concentration were recorded from bundles loaded with the fluorescent dye fura-PE3. RESULTS: Detrusor smooth muscles had two types of spontaneous electrical activity, i.e. individual and bursting action potentials. Ni(2+) (30 microM), a blocker for T-type Ca(2+) channels, reduced the frequency of individual action potentials without changing their amplitude. Higher concentrations of Ni(2+) (100-300 microM) converted individual action potentials into the bursts, as did apamin (0.1 microM), a blocker of small-conductance Ca(2+)-activated K(+) channels (SK). They also increased the amplitudes of spontaneous Ca(2+) transients and corresponding contractions whilst reducing their frequencies. In preparations which generated bursting action potentials, nifedipine (1 microm) converted action potentials into spontaneous transient depolarizations (STDs), and subsequent applications of Ni(2+) (100 microm) abolished STDs. Gadolinium (100 microM) and SKF96365 (10 microM), blockers for nonselective cation channels, and niflumic acid (100 microm), a blocker for Ca(2+)-activated Cl- channels, had no effect on either the amplitude or frequency of spontaneous action potentials. CONCLUSIONS: The T-type Ca(2+) channel may have dual roles in generating spontaneous excitation in detrusor smooth muscles. First, activity of these channels may account for the preceding depolarizations that lead to action potentials. Second, Ca(2+) influx through T-type Ca(2+) channels may couple functionally to SK channels, contributing to the stability of the resting membrane potential in detrusor smooth muscle. Thus, pharmacological manipulation of T-type Ca(2+) channels in detrusor smooth muscles could be of potential value for treating the overactive bladder.

Au(III), Pd(II), Ni(II), and Hg(II) alter NF kappa B signaling in THP1 monocytic cells.

The transcription factor NFkappaB plays a key role in the tissue inflammatory response. Metal ions released into tissues from biomaterials (e.g., Au, Pd, Ni, Hg) are known to alter the binding of NFkappaB proteins to DNA, thereby modulating the effect of NFkappaB on gene activation and, ultimately, the tissue response to biomaterials. Little is known about the effect of these metals on key signaling steps prior to NFkappaB-DNA binding such as transcription factor activation or nuclear translocation, yet these steps are equally important to modulation of the pathway. Oxidative stress is known to alter NFkappaB proteins and is suspected to play a role in metal-induced NFkappaB signaling modulation. Our aim in the current study was to assess the effects of sublethal levels of Ni, Hg, Pd, and Au ions on NFkappaB activation and nuclear translocation in the monocyte, which is acknowledged as an important orchestrator of the biological response to materials and the pathogenesis of chronic disease. Sublethal concentrations of Au(III), Ni(II), Hg(II), and Pd(II) were added to cultures of human THP1 monocytic cells for 72 h. In parallel cultures, lipopolysaccharide (LPS) was added for the last 30 min to activate the monocytic cells. Then cellular cytoplasmic and nuclear proteins were isolated, separated by electrophoresis, and probed for IkappaBalpha degradation (activation) and NFkappaB p65 translocation. Protein levels were digitally quantified and statistically compared. The levels of reactive oxygen species (ROS) in the monocytic cells were measured as a possible mechanism of metal-induced NFkappaB modulation. Only Au(III) activated IkappaBalpha degradation by itself. Au(III) and Pd(II) enhanced LPS-induced IkappaBalpha degradation, but Hg(II) and Ni(II) suppressed it. Au(III), Ni(II), and Pd(II) activated p65 nuclear translocation without LPS, and all but Ni(II) enhanced LPS-induced translocation. Collectively, the results suggest that these metal ions alter activation and translocation of NFkappaB, each in a unique way at unique concentrations. Furthermore, even when these metals had no overt effects on signaling by themselves, all altered activation of signaling by LPS, suggesting that the biological effects of these metals on monocytic function may only be manifest upon activation. None of the metal ions elevated levels of ROS at 72 h, indicating that ROS were probably not direct modulators of the NFkappaB activation or translocation at this late time point.

Contrasting effects of Cd2+ and Co2+ on the blocking/unblocking of human Cav3 channels.

Inorganic ions have been used widely to investigate biophysical properties of high voltage-activated calcium channels (HVA: Ca(v)1 and Ca(v)2 families). In contrast, such information regarding low voltage-activated calcium channels (LVA: Ca(v)3 family) is less documented. We have studied the blocking effect of Cd2+, Co2+ and Ni2+ on T-currents expressed by human Ca(v)3 channels: Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3. With the use of the whole-cell configuration of the patch-clamp technique, we have recorded Ca2+ (2 mM: ) currents from HEK-293 cells stably expressing recombinant T-type channels. Cd2+ and Co2+ block was 2- to 3-fold more potent for Ca(v)3.2 channels (EC50 = 65 and 122 microM, respectively) than for the other two LVA channel family members. Current-voltage relationships indicate that Co2+ and Ni2+ shift the voltage dependence of Ca(v)3.1 and Ca(v)3.3 channels activation to more positive potentials. Interestingly, block of those two Ca(v)3 channels by Co2+ and Ni2+ was drastically increased at extreme negative voltages; in contrast, block due to Cd2+ was significantly decreased. This unblocking effect was slightly voltage-dependent. Tail-current analysis reveals a differential effect of Cd2+ on Ca(v)3.3 channels, which can not close while the pore is occupied with this metal cation. The results suggest that metal cations affect differentially T-type channel activity by a mechanism involving the ionic radii of inorganic ions and structural characteristics of the channels pore.

Functional specialization of presynaptic Cav2.3 Ca2+ channels.

Ca2+ influx into presynaptic terminals via voltage-dependent Ca2+ channels triggers fast neurotransmitter release as well as different forms of synaptic plasticity. Using electrophysiological and genetic techniques we demonstrate that presynaptic Ca2+ entry through Cav2.3 subunits contributes to the induction of mossy fiber LTP and posttetanic potentiation by brief trains of presynaptic action potentials while they do not play a role in fast synaptic transmission, paired-pulse facilitation, or frequency facilitation. This functional specialization is most likely achieved by a localization remote from the release machinery and by a Cav2.3 channel-dependent facilitation of presynaptic Ca2+ influx. Thus, the presence of Cav2.3 channels boosts the accumulation of presynaptic Ca2+ triggering presynaptic LTP and posttetanic potentiation without affecting the low release probability that is a prerequisite for the enormous plasticity displayed by mossy fiber synapses.

Induction of apoptosis by S-nitrosoglutathione and Cu2+ or Ni2+ ion through modulation of bax, bad, and bcl-2 proteins in human colon adenocarcinoma cells.

In this study, the amount of S-nitrosoglutathione (GSNO) was measured spectrophotometrically at 334 nm. A spontaneous decrease in absorbency at 334 nm was detected when GSNO was exposed to 37 degrees C and a high pH (pH 8.0). We investigated the catalytic roles of various metal ions on the decomposition of GSNO. The degradation of GSNO (0.5 mM) was enhanced by the presence of Cu(2+) and Ni(2+) ions. The amount of nitric oxide (NO) released from GSNO degradation was estimated by the Griess reaction based on nitrite accumulation. The results indicated that nitrite production was elevated at least twofold in the presence of Cu(2+). Our study further indicated that Cu(2+) enhanced GSNO-induced apoptosis in human colon adenocarcinoma HT 29 cells. We also found that copper ions modulated the expression of bad, bax, and bcl-2 in GSNO-treated HT 29 cells. The levels of bax and bad proteins in treated cells were significantly elevated about fourfold to sixfold when compared with mock-treated cells 24 h after combined treatment with GSNO plus Cu(2+) or Ni(2+). On the other hand, significant inhibition of bcl-2 occurred in HT 29 cells with simultaneous treatment of GSNO with Cu(2+) (or Ni(2+)). It seemed that Cu(2+) and Ni(2+) can enhance the decomposition of GSNO, which liberates NO to activate the pathways. Our results demonstrated that the apoptotic effects induced by GSNO were promoted by Ni(2+) and Cu(2+) through two different mechanisms: depletion of intracellular glutathione and triggering of NO release from GSNO, which then promotes NO-induced apoptosis in human cells.

Nickel biochemistry.

Significant advances have been made in the past year in our understanding of the structure, function, and mode of regulation and assembly of nickel-containing enzymes. The highlight of 1997 was the elucidation of the methyl-CoM reductase structure.

Transcriptional and post-transcriptional regulation by nickel of sodN gene encoding nickel-containing superoxide dismutase from Streptomyces coelicolor Müller.

A novel type of superoxide dismutase containing nickel as a cofactor (NiSOD) has been discovered in several Streptomyces spp. The gene for NiSOD (sodN) was cloned from S. coelicolor Müller using degenerate oligonucleotide probes designed from the N-terminal peptide sequence of the purified enzyme. It encodes a polypeptide of 131 amino acids (14703 Da), without any apparent sequence similarity to other known proteins. The N-terminus of the purified NiSOD was located 14 amino acids downstream from the initiation codon of the deduced open reading frame (ORF), indicating the involvement of protein processing. The molecular mass of the processed polypeptide was predicted to be 13201 Da, in close agreement with that of the purified NiSOD (13.4 kDa). The transcription start site of the sodN gene was determined by S1 mapping and primer extension analysis. Ni2+ regulates the synthesis of NiSOD polypeptide. S1 mapping of both 5' and 3' ends of sodN mRNA revealed that Ni2+ increased the level of monocistronic sodN mRNA by more than ninefold without changing its half-life, thus demonstrating that Ni2+ regulates transcription. Both precursor and processed NiSOD polypeptides with little SOD activity were produced from the cloned sodN gene in S. lividans in the absence of sufficient Ni2+; however, on addition of Ni2+, active NiSOD consisting of only processed polypeptide was formed. Expression of the full-length sodN gene in E. coli produced NiSOD polypeptide without any SOD activity even in the presence of Ni2+. However, deletion of nucleotides encoding the N-terminal 14 amino acids from the sodN gene allowed the production of active NiSOD in E. coli, indicating that N-terminal processing is required to produce active NiSOD. These results reveal the unique role of nickel as a multifaceted regulator in S. coelicolor controlling sodN transcription and protein processing, as well as acting as a catalytic cofactor.

Nickel deficiency alters liver lipid metabolism in rats.

The present investigation was designed to examine the effect of nickel deficiency on lipid metabolism in liver and serum lipoproteins of rats. Therefore, a study over two generations was conducted feeding a nickel-deficient diet containing 13 microg/kg nickel or a nickel-adequate diet supplemented with 1 mg/kg nickel. Male 7-wk-old pups from the second offspring were studied. Pups fed a diet poor in nickel tended to have lower weight gains (P < 0.15), nickel concentrations in liver (P < or = 0.1) and iron levels in serum (P < 0.1) than nickel-adequate rats. They were classified as nickel-deficient on the basis of significantly lower erythrocyte counts, hemoglobin concentrations, hematocrits and nickel concentrations in kidney compared with nickel-adequate rats. Nickel deficiency caused a significant triacylglycerol accumulation in liver, with greater concentrations of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids than nickel-adequate rats. Nickel deficiency had slight but significant effects on the fatty acid composition of liver total lipids and phosphatidylcholine and phosphatidylethanolamine. Moreover, nickel-deficient rats had significantly lower activities of the lipogenic enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and fatty acid synthase than nickel-adequate rats. Nickel-depleted pups had significantly higher concentrations of triacylglycerols and phospholipids in serum VLDL, and cholesterol in serum LDL than nickel-adequate pups. Most of these alterations in lipid metabolism are similar to those obtained in several iron-deficiency studies. Because nickel deficiency also slightly compromised iron status, it is possible that at least some of the observed alterations are due to the moderate iron deficiency.