Glyoxalase I phenotype as a potential risk factor for prostate carcinoma

Samadi, Albert A.; Fullerton, Sean; Tortorelis, Dean G.; Johnson, G. Blake; Davidson, Scott D.; Choudhury, Muhammad; Mallouh, Camille; Tazaki, Hiroshi; Konno, Sensuke

doi:10.1016/s0090-4295(00)00874-8

Cited by 22 publications

(11 citation statements)

References 18 publications

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“…This deviation from Hardy-Weinberg equilibrium, which has been also reported in other populations (43), suggests the existence of yet unknown selection forces. Of note, this SNP has also been associated with diseases leading to decreased life expectancy such as prostate cancer and diabetes (44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Role for glyoxalase I in Alzheimer's disease

Chen

Wollmer

Hoerndli

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

146

101

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P301L mutant tau transgenic mice develop neurofibrillary tangles, a histopathologic hallmark of Alzheimer's disease and frontotemporal dementia (FTDP-17). To identify differentially expressed genes and to gain insight into pathogenic mechanisms, we performed a stringent analysis of the microarray dataset obtained with RNA from whole brains of P301L mutant mice and identified a single up-regulated gene, glyoxalase I. This enzyme plays a critical role in the detoxification of dicarbonyl compounds and thereby reduces the formation of advanced glycation end products. In situ hybridization analysis revealed expression of glyoxalase I in all brain areas analyzed, both in transgenic and control mice. However, levels of glyoxalase I protein were significantly elevated in P301L brains, as shown by Western blot analysis and immunohistochemistry. Moreover, a glyoxalase I-specific antiserum revealed many intensely stained flame-shaped neurons in Alzheimer's disease brain compared with brains from nondemented controls. In addition, we examined a single nucleotide polymorphism predicting a nonconservative amino acid substitution at position 111 (E111A) in ethnically independent populations. We identified significant and consistent deviations from HardyWeinberg equilibrium, which points to the presence of selection forces. The E111A single nucleotide polymorphism was not associated with the risk for Alzheimer's disease in the overall population. Together, our data demonstrate the potential of transcriptomics applied to animal models of human diseases. They suggest a previously unidentified role for glyoxalase I in neurodegenerative disease. A lzheimer's disease (AD) and frontotemporal dementia are common forms of age-related dementing diseases. They are characterized by proteinaceous aggregates, which are resistant to proteolysis due to conformational changes and posttranslational modifications such as hyperphosphorylation and glycation (1-4). In AD, these aggregates are ␤-amyloid plaques and neurofibrillary tangles (NFT). NFT formation, in the absence of overt amyloid plaques, is found in a group of neurodegenerative diseases, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (5, 6). In affected cells, the microtubule-associated protein tau is abnormally phosphorylated and relocalized from axonal to somatodendritic compartments, where it accumulates in aggregates that eventually assemble into NFT (7). The identification of mutations in the tau gene in FTDP-17 established that dysfunction of tau in itself can lead to dementia (6).NFT formation has been reproduced in transgenic mice by expression of FTDP-17 mutant tau, both in neurons (8-12) and in glial cells (13)(14)(15). Moreover, intracerebral injection of ␤-amyloid fibrils caused significant increases of NFT in the amygdala of P301L (FTDP-17) mutant mice (16). A similar increase was achieved by crossing ␤-amyloid-producing amyloid precursor protein mutant mice with P301L mice (17).The pathologic similarities between the P301L transgenic ...

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Section: Discussionmentioning

confidence: 99%

Role for glyoxalase I in Alzheimer's disease

Chen

Wollmer

Hoerndli

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

146

101

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“…These studies suggest that: (i) accumulation of glyoxalase I substrates is involved in the antitumour activity of important clinical antitumour agents (for example, doxorubicin), and (ii) further development of glyoxalase I inhibitors may provide antitumour agents active against some of the clinical tumours associated with high incidence and mortality rates (lung and prostate carcinomas). Further support for increased activity in this area of research comes from the link of increased glyoxalase I expression with invasive ovarian cancer in a proteomics study [61], a phenotypic link of glyoxalase I with prostate carcinoma [62], and high expression of glyoxalase I in human breast cancers [63].…”

Section: Overexpression Of Glyoxalase I and Mdr In Cancer Chemotherapmentioning

confidence: 99%

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

Thornalley

2003

Biochemical Society Transactions

116

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Glycation of nucleotides in DNA forms AGEs (advanced glycation end-products). Nucleotide AGEs are: the imidazopurinone derivative dG-G [3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxyimidazo[2,3-b]purin-9(8)one], CMdG ( N (2)-carboxymethyldeoxyguanosine) and gdC (5-glycolyldeoxycytidine) derived from glyoxal, dG-MG [6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one], dG-MG(2) [ N (2),7-bis-(1-hydroxy-2-oxopropyl)deoxyguanosine] and CEdG [ N (2)-(1-carboxyethyl)deoxyguanosine] derived from methylglyoxal, and dG-3DG [ N (2)-(1-oxo-2,4,5,6-tetrahydroxyhexyl)deoxyguanosine] derived from 3-deoxyglucosone and others. Glyoxal and methylglyoxal induce multi-base deletions, and base-pair substitutions - mostly occurring at G:C sites with G:C-->C:G and G:C-->T:A transversions. Suppression of nucleotide glycation by glyoxalase I and aldehyde reductases and dehydrogenases, and base excision repair, protects and recovers DNA from damaging glycation. The effects of DNA glycation may be most marked in diabetes and uraemia. Mutations arising from DNA glycation may explain the link of non-dietary carbohydrate intake to incidence of colorectal cancer. Overexpression of glyoxalase I was found in drug-resistant tumour cells and may be an example of an undesirable effect of the enzymatic protection against DNA glycation. Experimental overexpression of glyoxalase I conferred resistance to drug-induced apoptosis. Glyoxalase I-mediated drug resistance was found in human leukaemia and lung carcinoma cells. Methylglyoxal-mediated glycation of DNA may contribute to the cytotoxicity of some antitumour agents as a consequence of depletion of NAD(+) by poly(ADP-ribose) polymerase, marked increases in triosephosphate concentration and increased formation of methylglyoxal. S - p -Bromobenzylglutathione cyclopentyl diester is a cell-permeable glyoxalase I inhibitor. It countered drug resistance and was a potent antitumour agent against lung and prostate carcinoma. Glyoxalase I overexpression was also found in invasive ovarian cancer and breast cancer.

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“…9,10 Abnormal expression of this system has been demonstrated in a number of cellular disorders, including cancer. [11][12][13][14][15] In particular, altered expression and activities of GI and GII have been documented in tumor urogenital tissues [12][13][14][15][16][17] and in prostate tumor cell lines compared with corresponding normal tissues. 18 These alterations are considered to be crucial for sustaining tumor viability/survival under an altering microenvironment with tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Alteration of glyoxalases gene expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

Antognelli

Buono²,

Baldracchini³

et al. 2007

Cancer Biology & Therapy

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Glyoxalase system, a ubiquitous detoxification pathway protecting against cellular damage caused by potent cytotoxic metabolites, is involved in the regulation of cellular growth. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Recently, we described a possible regulatory effect by estrogens on glyoxalase genes in human breast cancer cell lines. This result, along with those ones regarding changes in glyoxalases activity and expression in other human hormoneregulated cancers, such as prostate cancer, has prompted us to investigate whether also androgens, whose functional role in prostate cancer pathogenesis is well known, could modulate glyoxalases gene expression. Therefore, we treated LNCaP androgen-responsive and PC3 androgen-independent human prostate cancer cell lines with testosterone at the concentrations of 1 nM and 100 nM. After a two days treatment, glyoxalases mRNA levels as well as cell proliferation were evaluated by real-time RT-PCR analysis and [ 3 H]thymidine incorporation, respectively. Results pointed out that testosterone affects the expression of glyoxalase system genes and cell proliferation in a different manner in the two cell lines. The possibility that modulation of glyoxalase genes expression by testosterone is due to glyoxalases-mediated intracellular response mechanisms to the androgen-induced oxidative stress or to the presence of androgen response elements (ARE) in glyoxalase promoters are discussed. Knowledge regarding the regulation of glyoxalases by testosterone may provide insights into the importance of these enzymes in human prostate carcinomas in vivo.

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Glyoxalase I phenotype as a potential risk factor for prostate carcinoma

Cited by 22 publications

References 18 publications

Role for glyoxalase I in Alzheimer's disease

Role for glyoxalase I in Alzheimer's disease

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

Alteration of glyoxalases gene expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

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