Distribution and concentration of zinc in the subcellular fractions of benign hyperplastic and malignant neoplastic human prostate

Dhar, Nikita; Goel, Trilok Chandra; Dubé, Pascale; Chowdhury, A. Roy; Kar, Amiya B.

doi:10.1016/0014-4800(73)90073-7

Cited by 46 publications

(31 citation statements)

References 3 publications

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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). Lesser effects include airway inflammation and asthma (Murgia et al 2006) and potentially depression (Nowak et al 2005).…”

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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“…Mitochondria of all cells sequester a significant amount of the cellular zinc, which Dhar [14] estimates to be about 30% in human prostate. Despite this important relationship, little information exists concerning the mechanism of mitochondrial zinc uptake/ transport.…”

Section: Mitochondrial Zinc Transportmentioning

confidence: 99%

“…Therefore the cytosolic source of mitochondrial zinc is derived from mobile reactive ZnLigands that are 10 kDa or less and are capable of permeating the outer mitochondrial membrane pores. These low molecular weight ZnLigands (such as ZnMetallothionein, ZnCitrate, ZnAspartate, ZnHistidine) constitute the source of "mobile reactive zinc" for transport into the mitochondria [14][15][16][17][18]. This pool of zinc is probably in the low uM range.…”

Section: Mitochondrial Zinc Transportmentioning

confidence: 99%

Zinc as an anti-tumor agent in prostate cancer and in other cancers

Franklin¹,

Costello²

2007

Archives of Biochemistry and Biophysics

211

142

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Human prostate glandular epithelial cells have the unique capability of accumulating high levels of zinc. This is essential to inhibit m-aconitase activity so that citrate can accumulate for secretion into prostatic fluid, which is a major function of the prostate gland. As a result, the Krebs cycle is truncated with the consequence of the lost ATP production that would result from citrate oxidation. The cellular accumulation of zinc also inhibits mitochondrial terminal oxidation and respiration. In addition to these metabolic effects, zinc accumulation exhibits anti-proliferative effects via its induction of mitochondrial apoptogenesis. Zinc accumulation also inhibits the invasive/migration activities in malignant prostate cells. The anti-proliferative effects and the effects on invasion and migration occur through zinc activation of specific intracellular signaling pathways. Consequently, these effects impose anti-tumor actions by zinc. The ability of prostate cells to accumulate zinc is due to the expression and activity of the zinc uptake transporter, ZIP1. To avoid the anti-tumor effects of zinc, in prostate cancer the malignant prostate cells exhibit a silencing of ZIP1 gene expression accompanied by a depletion of cellular zinc. Therefore we regard ZIP1 as a tumor suppressor gene in prostate cancer. In addition to prostate cells, similar tumor suppressor effects of zinc have been identified in several other types of tumors. KeywordsZinc; prostate cancer; tumor suppressor; apoptosis; Krebs cycle; zinc transporter; intermediary metabolismThe physiology and biochemistry of zinc and its importance in normal cellular and bodily function has been the subject of numerous reviews [1][2][3][4]. The regulation and maintenance of a "normal" concentration and distribution of cellular zinc are essential to the function, metabolism, growth, proliferation and survival of cells. A significant clinical aspect of zinc is its role in the development and progression of malignancy. There is now compelling clinical and experimental evidence that zinc is an important factor in prostate cancer, and also in other types of cancer. In relation to essential tumor cell activities, the effects of zinc can be categorized as: intermediary metabolism and bioenergetics effects; motility and invasive effects; growth and proliferation effects. The actions of zinc on all three activities impose antitumor effects in malignant prostate cells and other tumor cells. This review will present the *Correspondence to: Renty B.

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“…However, Zn was found not only in prostatic glandular epithelium but also in the stromal component (Ide-Ektessabi et al 2002). Thus, the long-standing questions about the main pool and the local distribution of Zn in prostate tissue still remain open (Mawson and Fischer 1952;Hoare et al 1956;Siegal et al 1961;Kar and Chowdhury 1968;Dhar et al 1973;Morita 1981;Leake et al 1983;Tvedt et al 1989;Bataineh et al 2002;Franklin et al 2005).…”

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confidence: 99%

Age-related histological and zinc content changes in adult nonhyperplastic prostate glands

Zaichick

2013

AGE

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To clarify age-related histological and Zn content changes in nonhyperplastic adult prostate glands, a quantitative morphometric and energy-dispersive X-ray fluorescence analyses were performed. The prostates were obtained from autopsies of 63 subjects aged 21-70 years who died mainly from trauma. It was found that histologically normal prostate tissue undergoes substantial changes throughout aging. These changes are reflected in an increase of the percent volume of the glandular lumen for the third to fifth decades, reaching a maximum for the decade 41-50 years. Over the same period, the percent volume of the stroma remains steady, but the percent volume of epithelium decreases, approximately, linearly with age. The percent volume of glandular lumen (reflects the volume of prostatic fluid) in the prostate gland of men aged 41 to 50 years is 1.5-fold higher than that in men aged 21 to 30 years, but the epithelium/lumen (prostatic fluid) ratio is approximately twofold lower. This suggests that accumulation of the prostatic fluid develops from 30 to 50 years of age. This accumulation of the prostatic fluid results in an increase of the Zn mass fraction in the prostate. In turn, when the intraprostatic Zn level exceeds a certain level by the end of the fifth decade, it begins to work as a trigger for different factors, all of which increase the proliferation of stromal cells. Deductions from these results allow possible partial explanations of both relevant prostatic aging mechanisms and the effects of dietary interventions using supplementary Zn.

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Distribution and concentration of zinc in the subcellular fractions of benign hyperplastic and malignant neoplastic human prostate

Cited by 46 publications

References 3 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 as an anti-tumor agent in prostate cancer and in other cancers

Age-related histological and zinc content changes in adult nonhyperplastic prostate glands

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