Cadmium Impairs p53 Activity in HepG2 Cells

Urani, Chiara; Melchioretto, Pasquale; Fabbri, Marco; Bowe, Gerard; Maserati, Emanuela; Gribaldo, Laura

doi:10.1155/2014/976428

Cited by 34 publications

(22 citation statements)

References 35 publications

(54 reference statements)

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“…Exposure to Cd leads to the transformation of prostate epithelial cells and a significant upregulation of KRAS (>20-fold) as well as the downregulation of 12 miRNAs, with miR-373 exhibiting the largest (11-fold) downregulation, and only a slight (6-fold) increase in miR-9 [68]. Cd exposure also can upregulate miR-372, which affects p21Cip1/WAF-1 expression in hepatic cell lines [69]. Changes in p21 activity will in turn alter p53 activity.…”

Section: Cadmium-associated Changes In Mirna Expressionmentioning

confidence: 99%

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development

Wallace

Taalab

Heinze

et al. 2020

Cells

109

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Toxic metals are extensively found in the environment, households, and workplaces and contaminate food and drinking water. The crosstalk between environmental exposure to toxic metals and human diseases has been frequently described. The toxic mechanism of action was classically viewed as the ability to dysregulate the redox status, production of inflammatory mediators and alteration of mitochondrial function. Recently, growing evidence showed that heavy metals might exert their toxicity through microRNAs (miRNA)-short, single-stranded, noncoding molecules that function as positive/negative regulators of gene expression. Aberrant alteration of the endogenous miRNA has been directly implicated in various pathophysiological conditions and signaling pathways, consequently leading to different types of cancer and human diseases. Additionally, the gene-regulatory capacity of miRNAs is particularly valuable in the brain-a complex organ with neurons demonstrating a significant ability to adapt following environmental stimuli. Accordingly, dysregulated miRNAs identified in patients suffering from neurological diseases might serve as biomarkers for the earlier diagnosis and monitoring of disease progression. This review will greatly emphasize the effect of the toxic metals on human miRNA activities and how this contributes to progression of diseases such as cancer and neurodegenerative disorders (NDDs).

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Section: Cadmium-associated Changes In Mirna Expressionmentioning

confidence: 99%

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development

Wallace

Taalab

Heinze

et al. 2020

Cells

109

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“…22,23 Also, exposure to Cd in pregnant women has been associated with functional loss and compromised p53-mediated DNA damage repair resulting to increased risk of preeclampsia. 24,25…”

Section: Cadmium As Antimetabolite To Zincmentioning

confidence: 99%

Environmental cadmium exposure: a possible factor in the pathogenesis of preeclampsia

Nwobi

Owolabi²,

Sotunsa

et al. 2019

Int J Res Med Sci

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Cadmium is a toxic metal, an environmental contaminant and a multi-organ poison which has been implicated in the derangement of a number of biological and molecular systems. Exposure to cadmium is a serious global health threat particularly in developing countries and pregnant women are at great risk, This is because they have increased gastrointestinal absorption and retention of cadmium and the tendency for increased risk of complications owing to its toxic effects. Preeclampsia is a pregnancy complication characterized by the development of onset of hypertension and significant proteinuria after 20 weeks of gestation or during labour and/or within 48 hours of delivery. This pregnancy-specific syndrome is a leading cause of maternal death particularly in developing countries. Several reports have provided evidence of remote association between preeclampsia and cadmium but the mechanism of the involment of this toxic metal in this disease is still surrounded with uncertainty. Some possible mechanistic pathways such as induction of oxidative stress, acting as an antimetabolite to zinc and deregulation of epigenetic mechanisms have been elucidated in this article may be interconnected, work synergistically or act independently. However, pertinent to understand them in a bid to possibly prevent the disease or forestall its devastating consequences. Environmental cadmium exposure may be considered a factor that merits further serious attention in the continuous search for the precise an etiology of preeclampsia particularly in developing countries that experience uncontrolled cadmium release into the environment.

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“…This may result in genome instability and cancer occurrence (Spike and Wahl, 2011). It was showed that cadmium can have effect on the both structure and function of p53 through different mechanisms such as apoptosis (Ho, 2004;Urani et al, 2014). Cadmium can bind to thiol groups as well as substitute with zinc in structure of P53.…”

Section: Cadmium Genotoxicity and The Influence On P53 Proteinmentioning

confidence: 99%