DNA damage induced via independent generation of the radical resulting from formal hydrogen atom abstraction from the C1′-position of a nucleotide

AbstractBackground: Deoxyribonucleotide radicals resulting from formal C1′-hydrogen atom abstraction are important reactive intermediates in a variety of DNA-damage processes. The reactivity of these radicals can be affected by the agents that generate them and the environment in which they are produced. As an initial step in determining the factors that control the reactivity of these important radical species, we developed a mild method for their generation at a defined site within a biopolymer.Results: Irradiation of oligonucleotides containing a photolabile nucleotide produced C1'-DNA radicals. In the absence of potential reactants other than O2, approximately 90% of the damage events involve formation of alkaline-labile lesions, with the remainder resulting in direct strand breaks. The ratio of alkaline-labile lesions to direct strand breaks (∼ 9:1) is independent of whether the radical is generated in single-stranded DNA or double-stranded DNA. Strand damage is almost completely quenched under anaerobic conditions in the presence of low thiol concentrations. Competition studies with 02 indicate that the trapping rate of C1′-DNA radicals by β-mercaptoethanol is ∼ 1.1 x 107 M−1s−1Conclusions: The mild generation of the C1'-DNA radical in the absence of exogenous oxidants makes it possible to examine their intrinsic reactivity. In the absence of other reactants, the formation of direct strand breaks from C1′-radicals is, at most, a minor pathway. Competition studies between β-mercaptoethanol and 02 indicate that significantly higher thiol concentrations than those in vivo or some means of increasing the effective thiol concentration near DNA are needed for these reagents to prevent the formation of DNA lesions arising from the C1'-radical under aerobic conditions

Intrahippocampal glucocorticoids generated by 11β-HSD1 affect memory in aged mice

Abstract11Beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) locally amplifies active glucocorticoids within specific tissues including in brain. In the hippocampus, 11β-HSD1 messenger RNA increases with aging. Here, we report significantly greater increases in intrahippocampal corticosterone (CORT) levels in aged wild-type (WT) mice during the acquisition and retrieval trials in a Y-maze than age-matched 11β-HSD1−/− mice, corresponding to impaired and intact spatial memory, respectively. Acute stress applied to young WT mice led to increases in intrahippocampal CORT levels similar to the effects of aging and impaired retrieval of spatial memory. 11β-HSD1−/− mice resisted the stress-induced memory impairment. Pharmacologic inhibition of 11β-HSD1 abolished increases in intrahippocampal CORT levels during the Y-maze trials and prevented spatial memory impairments in aged WT mice. These data provide the first in vivo evidence that dynamic increases in hippocampal 11β-HSD1 regenerated CORT levels during learning and retrieval play a key role in age- and stress-associated impairments of spatial memory

RETRACTED Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure

This article is being retracted from the Biochemical Journal at the request of the authors. The authors willingly supported independent investigations, which have confirmed concerns regarding image duplications in Figures 3B and 5B in the original publication. The authors apologise for the inconvenience caused. The Editorial Board agrees with the decision to retract

Coating conductive or semiconductive materials by polymerization of monomers on the surfaces.

Conductive and semiconductive materials are coated with 0.1-100-μm polymer anticorrosive films by (1) grafting diazonium salts having groups that function as polymn. initiators onto the surface and (2) radical or ring-opening polymn. of the monomers on the surface. Thus, an Fe electrode was electrolytically grafted with p-BrCHMeC6H4N2BF4, and Me methacrylate was polymd. by ATRP on the grafted surface