In vitro evidence for CCl4 metabolites covalently bound to lipoprotein micelles

AbstractCCl4-induced impairment of the lipoprotein secretion pathway of intact rat hepatocytes was carried out using 14CCl4 to check the possibility of binding to lipoproteins by CCl4 metabolites. After separation of different cell suspension fractions by means of ultracentrifugation and chemical precipitation procedures, a significant amount of the radioisotope was found covalently bound to the lipid and protein components of low density lipoproteins. Suitable experiments demonstrated that the bound radioisotope was represented by CCl4 metabolites and not by unactivated CCl4

Controlling the Cassie-to-Wenzel Transition: an Easy Route towards the Realization of Tridimensional Arrays of Biological Objects

In this paper we provide evidence that the Cassie-to-Wenzel transition, despite its detrimental effects on the wetting properties of superhydrophobic surfaces, can be exploited as an effective micro-fabrication strategy to obtain highly ordered arrays of biological objects. To this purpose we fabricated a patterned surface wetted in the Cassie state, where we deposited a droplet containing genomic DNA. We observed that, when the droplet wets the surface in the Cassie state, an array of DNA filaments pinned on the top edges between pillars is formed. Conversely, when the Cassie-to-Wenzel transition occurs, DNA can be pinned at different height between pillars. These results open the way to the realization of tridimensional arrays of biological objects

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity