Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice

Fernandes, Gabriel; Nair, Madhavan; Onoé, Kazunori; Tanaka, Toshio; Floyd, R. A.; Good, Robert A.

doi:10.1073/pnas.76.1.457

Cited by 288 publications

(106 citation statements)

References 35 publications

(22 reference statements)

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“…Low zinc intake can lead to a dramatic loss in immune defense capacity (Fernandes et al 1979) through apoptosis of precursor T-and B-cells, which results in lymphopenia (Fraker 2005). Zinc levels have been linked to cancer, particularly cancer of the prostate (Dhar et al 1973;Franklin 1998, 2000;Platz and Helzlsouer 2001;Bataineh et al 2002;Ho 2004), and to neurodegenerative disease, including amyotrophic lateral sclerosis (Dupuis et al 2004;Ho 2004).…”

Section: Resultsmentioning

confidence: 99%

Zinc Regulates the Stability of Repetitive Minisatellite DNA Tracts During Stationary Phase

Kelly¹,

Jauert²,

Jensen

et al. 2007

Genetics

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Repetitive minisatellite DNA tracts are stable in mitotic cells but unstable in meiosis, altering in repeat number and repeat composition. As relatively little is known about the factors that influence minisatellite stability, we isolated mutations that destabilize a minisatellite repeat tract in the ADE2 gene of Saccharomyces cerevisiae. One mutant class exhibited a novel color segregation phenotype, ''blebbing,'' characterized by minisatellite instability during stationary phase. Minisatellite tract alterations in blebbing strains consist exclusively of the loss of one 20-bp repeat. Timing experiments suggest that these tract alterations occur only after cells have entered stationary phase. Two complementation groups identified in this screen have mutations in either the high-affinity zinc transporter ZRT1 or its zinc-dependent transcriptional regulator ZAP1. The Dzrt1 mutant specifically affects the stability of minisatellite tracts; microsatellites or simple insertions in the ADE2 reading frame are not destabilized by loss of ZRT1. The Dzrt1 blebbing phenotype is partially dependent on a functional RAD50. Zinc is known for its role as an essential cofactor in many DNAbinding proteins. We describe possible models by which zinc can influence minisatellite stability. Our findings directly implicate zinc homeostasis in the maintenance of genomic stability during stationary phase.

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Section: Resultsmentioning

confidence: 99%

Zinc Regulates the Stability of Repetitive Minisatellite DNA Tracts During Stationary Phase

Kelly¹,

Jauert²,

Jensen

et al. 2007

Genetics

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“…A decline in in vivo-generated cytotoxic Tkiller activity to allogenic tumour cells in Zn-deficient mice has been observed. Decreased NK cell activity and responses to cutaneous sensitization have been reported in Zndeficient mice (Fernandes et al, 1979). All these effects of Zn deficiency on immune functions in mice can be reversed with Zn supplementation.…”

Section: Zinc Deficiencymentioning

confidence: 99%

Zinc and immune function

2002

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It is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. Research has begun to clarify the molecular mechanisms underlying the action of zinc on the immune function. It is clear that this trace element has a broad impact on key immunity mediators, such as enzymes, thymic peptides and cytokines, explaining the paramount importance of zinc's status on the regulation of lymphoid cell activation, proliferation and apoptosis. Ongoing and future studies regarding the immunological status of zinc deficiency 'at risk' groups could lead to public health interventions with nutritional doses of zinc supplements to prevent alteration of the immune system and improve resistance to infections.

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“…The significance of events such as DNA fragmentation or chromosomal condensathis evidence for the induction of necrosis, demonstrating most tion [19,21,31]. Ca 2ϩ /Mg 2ϩ -dependent endonuclease, a candipronounced alterations of thymosin β4 and thymosin β10, date for production of DNA oligonucleosomal ladders, is inhib-GAGE, metallothionein and parathymosin remains to be clariited by zinc [16,32]. Zinc has been shown to inhibit the activity fied.…”

mentioning

confidence: 99%

“…Apoptosis feahave an elevated level of such 'programmed' cell death [15,16]. tures high molecular-mass DNA fragmentation, abnormal chro-…”

mentioning

confidence: 99%

Induction of necrosis by zinc in prostate carcinoma cells and identification of proteins increased in association with this induction

Iguchi

Hamatake

Ishida

et al. 1998

European Journal of Biochemistry

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Zinc exhibits inhibitory effects on apoptosis, and a deficiency in this metal generally causes this type of cell death to occur. In the present study, we found that exposure to zinc results in necrosis of prostate carcinoma cells. When zinc acetate was added to LNCaP or PC-3 cells in monolayer culture, they began to detach from the culture dishes, and viability was lost after 4Ϫ8 h. Most of the cell death was found to be due to necrosis as determined by double staining with fluorescein-isothiocyanate-labeled annexin V and ethidium bromide, and by detection of hypodiploid cells. Associated with the induction of necrosis was an increase in low molecular-mass proteins, identified by HPLC analysis to be thymosin β10, parathymosin and GAGE in LNCaP cells, and thymosin β4, parathymosin and metallothionein in PC-3. The time course of the increase of thymosin β10 in LNCaP cells and thymosin β4 in PC-3 cells was consistent with that of appearance of cell detachment and dead cells. These results indicate that zinc can induce necrosis and suggest that production of proteins including β-thymosins is involved in induction of processes leading to cell detachment.

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Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice

Abstract: Several immunologic features were analyzed in mice on a zinc-deficient diet [Zn(-)

Cited by 288 publications

References 35 publications

Zinc Regulates the Stability of Repetitive Minisatellite DNA Tracts During Stationary Phase

Zinc Regulates the Stability of Repetitive Minisatellite DNA Tracts During Stationary Phase

Zinc and immune function

Induction of necrosis by zinc in prostate carcinoma cells and identification of proteins increased in association with this induction

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