Zinc and Cadmium Complexes of a Plant Metallothionein under Radical Stress: Desulfurisation Reactions Associated with the Formation of trans‐Lipids in Model Membranes

Abstract

Metallothioneins (MTs) are sulfur-rich proteins capable of binding metal ions to give metal clusters. The metal-MT aggregates used in this work were Zn- and Cd-QsMT, where QsMT is an MT from the plant Quercus suber. Reactions of reductive reactive species (H(*) atoms and e(aq)(-)), produced by gamma irradiation of water, with Zn- and Cd-QsMT were carried out in both aqueous solutions and vesicle suspensions, and were characterized by different approaches. By using a biomimetic model based on unsaturated lipid vesicle suspensions, the occurrence of tandem protein/lipid damage was shown. The reactions of reductive reactive species with methionine residues and/or sulfur-containing ligands afford diffusible sulfur-centred radicals, which migrate from the aqueous phase to the lipid bilayer and transform the cis double bond of the oleate moiety into the trans isomer. Tailored experiments allowed the reaction mechanism to be elucidated in some detail. The formation of sulfur-centred radicals is accompanied by the modification of the metal-QsMT complexes, which were monitored by various spectroscopic and spectrometric techniques (Raman, CD, and ESI-MS). Attack of the H(*) atom and e(aq)(-) on the metal-QsMT aggregates can induce significant structural changes such as partial deconstruction and/or rearrangement of the metal clusters and breaking of the protein backbone. Substantial differences were observed in the behaviour of the Zn- and Cd-QsMT aggregates towards the reactive species, depending on the different folding of the polypeptide in these two cases.

Abnormal Blood Levels of Trace Elements and Metals, DNA Damage, and Breast Cancer in the State of Kuwait

“…The reason as to why high levels of Se were associated with micronucleus formation in the control group in the present study could not be explained. Lastly, we propose that the high blood levels of Cd in the breast cancer patients in our study was significantly associated with higher number of micronucleated binucleated lymphocytes for the following reasons: First, Cd has been found to have a very strong binding ability to intracellular polypeptides like metallothionines, thus preventing their ability to suppress the production of free radicals [85]. Second, biological antioxidants, such as cysteine and ascorbate, which normally play a protective role, can play a more damaging one in presence of Cd due to the production of ROS [86].…”

Analysis of serum levels of 15 trace elements in breast cancer patients in Shandong, China

“…High serum Ca levels may not only have tumor-protective effects by increasing cell differentiation, decreasing proliferation, and inducing apoptosis but also have tumor-promoting effects due to its association with parathyroid hormone and vitamin D. Cd induces genotoxicity by proto-oncogenes activation, apoptosis inhibition, induction of single-strand DNA breaks, and inactivation of mismatch repair system. Cd has strong binding ability to intracellular polypeptides to prevent them from suppressing production of free radicals (Torreggiani et al 2009). Li has selective anti-neoplastic properties against human breast cancer cell lines containing oncogenic PIK3CA mutations.…”

Biomimetic Chemistry: Radical Reactions in Vesicle Suspensions

“…Therefore, the presence of both sulfurcontaining amino acids and sulfide anions in the same molecular aggregate makes this system a very interesting case to determine the main targets of the reductive stress. Interestingly, a differentiation of reactivity can be assessed, since the reductive conditions seem to preferentially select the methionine and cysteine residues (Torreggiani et al, 2009). In all these experiments the protein damages were found to be coupled with the unsaturated lipid isomerisation and formation of trans fatty acids in the vesicles.…”