Dithiocarbamates Inhibit Hematopoiesis via a Copper-Dependent Mechanism

Pyatt, David W.; Yang, Yanzhu; Le, Anh‐Tuan; Stillman, Wayne S.; Irons, Richard D.

doi:10.1006/bbrc.2000.3149

Cited by 12 publications

(5 citation statements)

References 32 publications

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“…. Dithiocarbamates like diethyldithiocarbamate were designed as copper chelators, and it is well known that they are not specific inhibitors of Cu,Zn-SOD (24,25). Therefore, differences in the extent of inhibition of transition metal-dependent processes unrelated to Cu,Zn-SOD may explain the difference in IDO activity in rabbit enterocytes versus HAEC.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome b5, Not Superoxide Anion Radical, Is a Major Reductant of Indoleamine 2,3-Dioxygenase in Human Cells

Maghzal

Thomas

Hunt

et al. 2008

Journal of Biological Chemistry

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The heme protein indoleamine 2,3-dioxygenase (IDO) initiates oxidative metabolism of tryptophan along the kynurenine pathway, and this requires reductive activation of Fe . plays a major role in the activation of IDO in human cells.Human indoleamine 2,3-dioxygenase (IDO) 3 is a cellular enzyme that catalyzes the initial step of the oxidative metabolism of L-tryptophan (L-Trp) along the kynurenine pathway (1, 2). IDO cleaves the pyrrole ring of L-Trp to N-formyl-kynurenine by incorporating molecular oxygen. Although L-Trp is preferred, the enzyme can use other indoleamines such as tryptamine and serotonin as substrates. IDO is expressed constitutively in a limited number of human tissues (3) and also in rabbit enterocytes (4), but in most tissues and cells, expression of the enzyme requires induction, with the pro-inflammatory cytokine interferon-␥ (IFN␥) playing a major role (2). The true physiological function of IDO is becoming clearer, with its induction and the formation of kynurenine pathway metabolites implicated in various physiological and pathological processes, such as in the defense against microbes and tumors, immune regulation, neuropathology, and antioxidant activity (2).IDO is a monomeric protein of 42-kDa molecular mass and contains protoporphyrin IX as its sole prosthetic group (4).

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Section: Discussionmentioning

confidence: 99%

Cytochrome b5, Not Superoxide Anion Radical, Is a Major Reductant of Indoleamine 2,3-Dioxygenase in Human Cells

Maghzal

Thomas

Hunt

et al. 2008

Journal of Biological Chemistry

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“…Altogether, these data highlight that dis-regulation of NOS/NO system can dramatically affect reproductive performances in both male and female. Furthermore, it has been demonstrated that DTCBs can trigger cell apoptosis [92], and in particular induce a dose-related increase in bone marrow cell death [93] …”

Section: Will Be Famous: the Dithiocarbamatesmentioning

confidence: 99%

The Effects of the Endocrine Disruptors Dithiocarbamates on the Mammalian Ovary with Particular Regard to Mancozeb

Cecconi

Paro²,

Rossi³

et al. 2007

CPD

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Many human-made chemicals are called endocrine disruptors (EDs) because they have the potential to disrupt endocrine functions in exposed organisms. Many EDs can disrupt hormonal homeostasis by interfering with hormone receptor recognition, binding and activation, while others act by still unknown mechanisms. Among the EDs specifically affecting the female reproductive system, those with steroidogenic/antisteroidogenic effects have been extensively studied and the mechanisms of toxicity clarified also at molecular level. For many others, information is restricted to few epidemiological data and in vivo/in vitro experiments with animal models. This is the case of the dithiocarbamates, and in particular of the fungicide mancozeb, an ethylenedithiocarbamate widely used to protect fruit and vegetables, ginseng included, because of its low acute toxicity in humans. Although the mechanism(s) by which mancozeb may specifically act on female reproductive organs are largely unknown, data on experimental animals in vivo have demonstrated that the fungicide can induce several disturbances on estrus cycle. When used in vitro at concentrations considered too low to cause human health injuries, the fungicide impairs mouse embryo development and meiotic spindle assembly. The possibility that the female germ cell (the oocyte) could be a specific target of mancozeb suggests a role for this fungicide as probable inductor of infertility also in exposed human populations.

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“…42,43 Disulfiram-mediated apoptosis has been shown to occur in thymocytes, 75 smooth muscle cells 76 and human hepatoma cells. 77 There is evidence that disulfiram induces p53. 78,79 The modulation of p53 occurs at an early stage in the apoptotic pathway, resulting in inhibition of bcl-2 79 and subsequent apoptosis.…”

Section: Use Of Disulfiram As An Anticancer Agentmentioning

confidence: 99%

Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections

2005

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Dithiocarbamates Inhibit Hematopoiesis via a Copper-Dependent Mechanism

Cited by 12 publications

References 32 publications

Cytochrome b5, Not Superoxide Anion Radical, Is a Major Reductant of Indoleamine 2,3-Dioxygenase in Human Cells

Cytochrome b5, Not Superoxide Anion Radical, Is a Major Reductant of Indoleamine 2,3-Dioxygenase in Human Cells

The Effects of the Endocrine Disruptors Dithiocarbamates on the Mammalian Ovary with Particular Regard to Mancozeb

Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections

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