The carcinogenicity of certain nickel compounds has been confirmed by the combination of epidemiological evidence in humans and carcinogenesis bioassays in animals. The molecular mechanisms of nickel-induced carcinogenesis include interactions of this metal with major chromatin components causing alterations in gene expression rather than by direct DNA damage. Nickel, amongst 12 different metals, specifically induces a cytoplasmatic protein called Cap43, whose role is not clear, but it has been connected to hypoxia and is overexpressed in a number of cancer cells. Its most interesting feature is a monohistidine decapaptide repeated consecutively three times at the C-terminus, TRSRSHTSEG-TRSRSHTSEG-TRSRSHTSEG. Ni(II) is able to efficaciously and multiply bind to this sequence, and every single decapeptide fragment can anchor one metal ion. So, a detoxification role for Cap43 cannot be excluded [1-6]. Last, but not least, nickel intolerance is a very well known cause of allergies and skin rashes. It has been discovered that this may be due to nickel interaction with a specific protein, called Toll-like receptor, which shows in its sequence a histidine residue that is not present in the rat homologue, for instance, as in other animals not suffering from nickel allergies. It is thus possible that specific histidine in the human variant is the responsible for nickel intolerance, since this metal can bind it in a very effective way (Fig.1) . In this lecture we want to give an overview on nickel interesting behaviour inside the human organism by describing the most recent findings on the topics described above.
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|Titolo:||Toxic and Carcinogenic Effects of Nickel Interaction with Histidine Rich Peptides|
|Data di pubblicazione:||2014|
|Appare nelle tipologie:||4.2 Abstract in Atti di convegno|