Transition metal-induced apoptosis in lymphocytes via hydroxyl radical generation, mitochondria dysfunction, and caspase-3 activation: an in vitro model for neurodegeneration

Rio, Marlene Jimenez Del; Vélez-Pardo, Carlos

doi:10.1016/j.arcmed.2004.01.001

Cited by 53 publications

(21 citation statements)

References 46 publications

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“…Bergman et al 2005; Bidle and Bender 2008; Brard et al 2006; Buss et al 2003; Fukuchi et al 1994; Greene et al 2002; Haq et al 1995; Hileti et al 1995; Jiang et al 2002; Jin et al 2007; Koc et al 2006; Kovář et al 1997, 2001; Leardi et al 1998; Lee et al 2006b, c; Pan et al 2004; Simonart et al 2000; Sun et al 2009; Truksa et al 2003; Zhang et al 2003; Zhao et al 2004) or in excess (e.g. Aljandali et al 2001; Cozzi et al 2003, 2010; Devireddy et al 2005; Franke et al 2010; Jacob et al 1997, 2000; Javadi et al 2004; Jímenez Del Río and Vélez-Pardo 2004; Kamp et al 2002; Kawabata et al 1997; Kermer et al 2004; Kooncumchoo et al 2006; Kruman et al 1997; Kummer et al 2008; Kurz et al 2007, 2008b; Lakshmi Devi and Anuradha 2009; Lee et al 2006d; Levenson 2005; Lu et al 2008; Ma et al 2009; Messer et al 2009; Murakami et al 2006; Natoli et al 2009; Persson 2005; Polla et al 2003; Schlawe et al 2004; Shin and Kim 2009; Shukla et al 2003; Tenopoulou et al 2005; Upadhyay and Kamp 2003; Vélez-Pardo et al 1997; Zhao et al 1997). …”

Section: Apoptosis or Necrosis?mentioning

confidence: 99%

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

2010

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Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions.

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Section: Apoptosis or Necrosis?mentioning

confidence: 99%

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

2010

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“…In case of cadmium, metallothionein expression determines the cell death fate (between apoptosis and necrosis), but Cd-induced apoptosis is due to inhibition of antioxidant enzymes, mitochondrial dysfunction [104], and PTP opening, probably through its interaction with thiol groups of ANT [105], whereas ROS and p53 contribute to apoptosis caused by chromium and selenium [106–108]. In addition, PM containing high levels of noncarcinogenic metals (i.e., cobalt, lead, iron, and zinc) were often shown to provoke ROS production (e.g., H 2 O 2 ) leading to apoptosis through the mitochondrial pathway [109–113]. Under apoptotic conditions, zinc is also able to increase p53 expression and function probably by stabilizing this protein which contains a tightly bound zinc atom necessary for its DNA binding activity [114, 115].…”

Section: Air Pollutants and Cytotoxic Cell Deathmentioning

confidence: 99%

Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

Andréau

Leroux

Bouharrour

2012

Biochemistry Research International

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Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

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“…Likewise in THP-1 cells, no significant change was observed in DNA binding by NF-κB after exposure to 50, 200 or 400 µM copper 25; 26. No change in the nuclear localization of NF-κB was observed using primary human peripheral blood lymphocytes treated with 500 µM copper 27. It is important to note that these studies were performed using lymphocyte derived cells, which are not responsible for maintaining copper homeostasis at the organismal level.…”

Section: Discussionmentioning

confidence: 91%

“…The effect of copper on NF-κB activation is also unresolved. Some groups have reported activation of NF-κB by copper 20; 21; 22, whereas others report that copper reduces or has no effect on NF-κB activity 23; 24; 25; 26; 27. In the analysis of the copper-treated HepG2 cell transcriptome, the NF-κB signaling pathway was identified as one that was activated in response to copper 16.…”

Section: Introductionmentioning

confidence: 99%

Copper Activation of NF-κB Signaling in HepG2 Cells

McElwee¹,

Song²,

Freedman³

2009

Journal of Molecular Biology

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SUMMARYCopper is a persistent environmental contaminant, and exposure to elevated levels of this transition metal can result in a variety of pathologies. To protect against metal-induced pathologies, copper affects the transcription of multiple defense and repair genes. To better understand the mechanisms by which copper affects the transcription of stress-responsive genes, HepG2 cells were treated with copper under multiple conditions and microarray analyses were previously performed. Analysis of the microarray data indicated that copper modulates multiple signal transduction pathways, including those mediated by NF-κB. Luciferase assays, quantitative RT-PCR and chemical inhibition in HepG2 cells validated the microarray results and confirmed that NF-κB was activated by stress-inducible concentrations of copper. In addition, two novel NF-κB-regulated genes, SRXN1 and ZFAND2A were identified. Our results indicate that the activation of NF-κB may be important for survival under elevated concentrations of copper.

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Transition metal-induced apoptosis in lymphocytes via hydroxyl radical generation, mitochondria dysfunction, and caspase-3 activation: an in vitro model for neurodegeneration

Cited by 53 publications

References 46 publications

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

Copper Activation of NF-κB Signaling in HepG2 Cells

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