New roles for quin2: Powerful transition-metal ion chelator that inhibits copper-, but potentiates iron-driven, fenton-type reactions

Sandström, B; Granström, Micael; Marklund, Stefan L.

doi:10.1016/0891-5849(94)90141-4

Cited by 20 publications

(16 citation statements)

References 32 publications

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“…2A), the effect of C a E D TA does not involve its possible chemical interaction with STZ. The effect of CaEDTA is not due to its possible chelation of iron, which has a higher affinity for EDTA than C a 2 + (15), because EDTA chelation of iron does not inhibit radical generation through Fenton reaction (19,20). However, the possibility that the capture of Fe ion by EDTA might be involved in the protection of islet cells from free radical injury cannot be completely excluded because of the complexity of FeEDTA effects on free radical reactions.…”

Section: Discussionmentioning

confidence: 99%

Zinc as a paracrine effector in pancreatic islet cell death.

Kim

et al. 2000

Diabetes

100

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Because of a huge amount of Zn 2 + in secretory granules of pancreatic islet -cells, Zn 2 + released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn 2 + on -cell death. Zn 2 + induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn 2 + by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Z n 2 + chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-( 6 -m e t h o x y -q u i n o l y l ) -p a r a -t o l u e n esulfonamide staining revealed that Zn 2 + was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn 2 + is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, which in time might contribute to the development of diabetes in aged people. D i a b e t e s 4 9 :3 6 7-372, 2000 C ertain central neurons and pancreatic islet -c e l l s contain a substantial amount of chelable zinc ion ( Z n 2 + ) (1,2). Neuronal Zn 2 + is co-secreted with neurotransmitters after excitation and might be involved in the modulation of ion channel activity (3,4). R e c e n t l y, reports indicating a role of endogenous Zn 2 + in neuronal death were published. First, in vitro treatment with Z n 2 + induced neuronal cell death (5,6). Second, Zn 2 + , highly concentrated in synaptic vesicles of neurons (7), was shown to be translocated to degenerating postsynaptic neurons after cerebral ischemia or prolonged seizure (8,9). Finally, administration of a Zn 2 + chelator abrogated ischemic neuronal injury (10). These findings suggest that Zn 2 + in synaptic vesicles may be causally related to neuronal death. Similar phenomena may occur in pancreatic -cells. Islet -cells contain even more Zn 2 + than do neurons. Zn 2 + in -cells, involved in the formation of insoluble insulin hexamer in secretory granules (11,12), is also co-secreted with insulin after stimulation with secretagogues (13). Zn 2 + released in certain conditions may have an impact on pancreatic -cells if significant local concentration is achieved. The current work was carried out to explore this possibility, focusing on the role of Zn 2 + in islet cell death. RESEARCH DESIGN AND METHODSCell culture. MIN6N8 cells, SV40-transformed insulinoma cells (14) (kindly provided by Prof. Miyazaki, Osaka University, Osaka, Japan), were cultured in Dulb e c c o 's modified Eagle's medium (DMEM) (GibcoBRL, Rockville, MD)-15% fetal calf serum (FCS). The effect of Zn 2 + was examined by culturing cells in the presence of ZnSO 4 . The presence of ZnSO 4 up to 1 mmol/l did not significantly affect pH of the culture medium. In experiments studying the effect of Zn 2 + without binding to proteins or amino acids, control salt solution (...

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Section: Discussionmentioning

confidence: 99%

Zinc as a paracrine effector in pancreatic islet cell death.

Kim

et al. 2000

Diabetes

100

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“…Superoxide radicals are converted into hydroxyl radicals in the presence of redox-active metal ions, including Fe$ + and Cu# + [10]. As hydroxyl radicals are highly reactive and will induce oxidative damage to biomolecules, including DNA, particular attention has been focused in recent years on the relative importance of direct free-radical-mediated reactions and calcium-dependent processes in cell killing during oxidative stress [11][12][13][14]. Recent findings indicate that both mechanisms of cell killing may operate, depending on the level of oxidant present.…”

Section: Introductionmentioning

confidence: 99%

1,10-Phenanthroline stimulates internucleosomal DNA fragmentation in isolated rat-liver nuclei by promoting the redox activity of endogenous copper ions

Burkitt¹,

Milne²,

Nicotera

et al. 1996

Biochemical Journal

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Isolated rat-liver nuclei were incubated with a series of membrane-permeable metal-ion-complexing agents and examined for DNA damage. Of the reagents tested, only 1,10-phenanthroline (OP) and neocuproine (NC) were found to induce DNA fragmentation. Agarose-gel electrophoresis of the DNA fragments generated in the presence of OP revealed internucleosomal cleavage, which is widely considered to be a hallmark for the enzymic DNA digestion that occurs during apoptosis. Ascorbate, particularly in the presence of hydrogen peroxide, increased the levels of fragmentation induced by OP. As well as undergoing fragmentation, the DNA from nuclei was also found to contain 8-hydroxydeoxyguanosine, which indicates attack (oxidation) by the hydroxyl radical. Complementary experiments in vitro involving ESR determinations of hydroxyl radical formation and measurements of DNA oxidation under biomimetic conditions demonstrated that Cu2+, but not Fe3+, forms a complex with either OP or NC (but not the other complexing agents tested) that stimulates hydroxyl radical formation and DNA damage in the presence of hydrogen peroxide and ascorbate. It is therefore proposed that OP in the nuclei incubations binds to Cu2+, which exists naturally in chromosomes, forming a complex that promotes hydroxyl-radical-dependent DNA fragmentation. These findings demonstrate the promotion of hydroxyl-radical-mediated DNA damage by endogenous Cu2+ and, perhaps more significantly, demonstrate that the internucleosomal DNA 'laddering' that is often used as an indicator of apoptosis may also result from DNA fragmentation by non-enzymic processes.

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“…In contrast, Ar + is more likely to cause heavy damage via single-and double-strand breaks in DNA. The in vitro and in vivo effects of �arious ions on DNA breakage and mutation ha�e been pre�iousl� confirmed (Nordhoff et al, 1993;Sandstrom et al, 1994;Kiefer et al, 2002;Liu et al, 2003), but our results suggest that N + is the optimal ion for inducing mutations in microorganisms. A highly active, thermostable α�am�lase �ould be beneficial to the fermentation industry.…”

Section: Discussionmentioning

confidence: 69%

Improved thermostable α-amylase activity of Bacillus amyloliquefaciens by low-energy ion implantation

Zhang²,

Zhu³

2011

Genet. Mol. Res.

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ABSTRACT. Thermostable α-amylase is of great importance in the starch fermentation industry; it is extensively used in the manufacture of beverages, baby foods, medicines, and pharmaceuticals. Bacillus amyloliquefaciens produces thermostable α�am�lase� ho�e�er� produc� α�am�lase� ho�e�er� produc� -amylase; however, production of thermostable α-amylase is limited. Ion-beam implantation is an effective method for mutation breeding in microbes. We conducted ionbeam implantation experiments using two different ions, Ar + and N + , to determine the survival rate of and dose effect on a high α-amylase activity strain of B. amyloliquefaciens that had been isolated from soil samples. N + implantation resulted in a higher survival rate than Ar + implantation. The optimum implantation dose was 2.08 × 10 15 ions/ cm 2 . Under this implantation condition, we obtained a thermally and genetically stable mutant α-amylase strain (RL-1) with high enzyme activity for degrading α-amylase. Compared to the parental strain (RL), the RL-1 strain had a 57.1% increase in α-amylase activity. We conclude that ion implantation in B. amyloliquefaciens can produce strains with increased production of thermostable α-amylase.

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New roles for quin2: Powerful transition-metal ion chelator that inhibits copper-, but potentiates iron-driven, fenton-type reactions

Cited by 20 publications

References 32 publications

Zinc as a paracrine effector in pancreatic islet cell death.

Zinc as a paracrine effector in pancreatic islet cell death.

1,10-Phenanthroline stimulates internucleosomal DNA fragmentation in isolated rat-liver nuclei by promoting the redox activity of endogenous copper ions

Improved thermostable α-amylase activity of Bacillus amyloliquefaciens by low-energy ion implantation

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