Heavy Metal Ions in Normal Physiology, Toxic Stress, and Cytoprotection

Lynes, Michael A.; Kang, Yu; Sensi, Stefano L.; Perdrizet, George A.; Hightower, Lawrence E.

doi:10.1196/annals.1391.010

Cited by 64 publications

(64 citation statements)

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“…The exact pathogenesis is unknown but involves factors, such as genetic predisposition and alterations in the levels of neurotransmitters and some trace elements (8,13,14). There is a growing evidence that the balance between the bioelements, such as Mg, Ca, Fe, Cu, Zn, and Se in the nervous tissue is of crucial importance for maintaining human health (15). In biological systems, these mainly metallic elements are usually bound to proteins.…”

Section: Discussionmentioning

confidence: 99%

Major and minor bio-element status in children with febrile seizure

Akbayram¹,

Cemek²,

Büyükben³

et al. 2012

BLL

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Febrile seizures (FS) are the most common cause of seizures in children. The exact etiopathogenesis is unknown but involves factors like genetic predisposition and alterations in the levels of neurotransmitters and some trace elements. The study includes 48 consecutive children with FS, and 55 healthy age matched control subjects. Calcium, magnesium and potassium concentrations in the febrile study group were lower than in the control group (p<0.05). Iron and Gallium levels in the study group were lower than in the control group (p<0.01). Serum Selenium (p<0.001), Zinc (p<0.001) and Strontium (p<0.05) levels were signifi cantly decreased in the study group when compared to the control group. There was no signifi cant difference between the control and study groups in Serum Barium, Beryllium and Copper levels (p>0.05). The aim of the present prospective analytical case-control study was to determine whether there was any change in element levels in children with FS (Ref. 33). Full Text in PDF www.elis.sk.

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Section: Discussionmentioning

confidence: 99%

Major and minor bio-element status in children with febrile seizure

Akbayram¹,

Cemek²,

Büyükben³

et al. 2012

BLL

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“…They function as metal homeostasis regulators for both essential and toxic metals (10)(11)(12). MT knockout mice are viable but sensitive to cadmium (Cd) and, to a lesser degree, copper (Cu), zinc (Zn), and mercury (13).…”

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confidence: 99%

Single nucleotide in the MTF-1 binding site can determine metal-specific transcription activation

Sims

Chirn

Marr

2012

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

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Cells respond to changes in environment by shifting their gene expression profile to deal with the new conditions. The cellular response to changes in metal homeostasis is an important example of this. Transition metals such as iron, zinc, and copper are essential micronutrients but other metals such as cadmium are simply toxic. The cell must maintain metal concentrations in a window that supports efficient metabolic function but must also protect against the damaging effects of high concentrations of these metals. One way a cell regulates metal homeostasis is to control genes involved in metal mobilization and storage. Much of this regulation occurs at the level of transcription and the protein most responsible for this is the conserved metal responsive transcription factor 1 (MTF-1). Interestingly, the nature of the changes in the gene expression profile depends on the type of exposure. The cell somehow senses the kind of the metal challenge and responds appropriately. We have been using the Drosophila system to try to understand the mechanism of this metal discrimination. Using genome-wide mapping of MTF-1 binding under different metal stresses we find that, surprisingly, MTF-1 chooses different DNA binding sites depending on the specific nature of the metal insult. We also find that the type of binding site chosen is an important component of the capability to induce the metal-specific transcription activation.heavy metal | MED26 D NA recognition by sequence-specific DNA binding transcription factors is the basic mechanism that links the cisregulatory information encoded in the genome with transcriptional control of gene expression. Although it is the DNA binding domain of these factors that dictates the sequence element bound by the protein, it is now clear that, at least for some factors, the DNA sequence of the binding site itself can influence the activation potential of the transcription factor (1, 2). Clearly the process of reading the genome and activating transcription is more intricate than a simple DNA binding event.Some transcription factors respond to signaling events and activate the transcription of different sets of genes in a signalspecific manner. The cellular response to changes in metal homeostasis is one example of this observation. The major transcription factor involved in metal homeostasis is the metal responsive element (MRE) binding transcription factor-1 (MTF-1) (for a recent review, see ref.3). MTF-1 is required for both constitutive and metal inducible transcription of some genes; it is also required for activated transcription of at least one gene in low metal conditions (4, 5). Thus, it responds to both excess and limiting metal conditions by activating different sets of genes.

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“…Indeed, the ability of mussels to up-regulate genes encoding heat-shock proteins does not seem to be compromised by Cd-exposure (Micovic et al, 2009). Besides, it is conceivable that Cdexposure might have facilitated the heat-shock response because Cd-response genes and HSP70 genes share a common regulatory mechanism (Lynes et al, 2007). This would explain the effective but promptly reversible response to heat-shock in Cd-exposed mussels and the return to lysosomal biomarker values characteristic of Cd-exposure alone.…”

Section: 2mentioning

confidence: 98%