Oxidative stress to promote cell death or survival

Editoria

Generation of human induced pluripotent stem cell lines (UNIMGi003-A and UNIMGi004-A) from two Italian siblings affected by Unverricht-Lundborg disease

Unverricht-Lundborg disease (ULD) is an inherited form of progressive myoclonus epilepsy caused by mutations in the gene encoding Cystatin B (CSTB), an inhibitor of lysosomal proteases. The most common mutation described in ULD patients is an unstable expansion of a dodecamer sequence located in the CSTB gene promoter. This expansion is causative of the downregulation of CSTB gene expression and, consequently, of its inhibitory activity. Here we report the generation of induced pluripotent stem cell (iPSC) lines from two Italian siblings having a family history of ULD and affected by different clinical and pathological phenotypes of the disease

Absolute rate constants for hydrogen atom transfer from tertiary amides to the cumyloxyl radical: evaluating the role of stereoelectronic effects

A time-resolved kinetic study of the hydrogen atom transfer (HAT) reactions from a series of alkanamides to the cumyloxyl radical (CumO\u2022) was carried out. With N,N-dialkylformamides HAT preferentially occurs from the formyl C-H bond, while in N-formylpyrrolidine HAT mostly occurs from the ring \u3b1-C-H bonds. With the acetamides and the alkanamides almost exclusive HAT from the C-H bonds that are \u3b1 to nitrogen was observed. The results obtained show that alignment between the C-H bond being broken and the amide \u3c0-system can lead to significant increases in the HAT rate constant (k H). This finding points toward the important role of stereoelectronic effects on the HAT reactivity and selectivity. The highest kH values were measured for the reactions of CumO\u2022 with N-acylpyrrolidines. These substrates have ring \u3b1-C-H bonds that are held in a conformation that is optimally aligned with the amide \u3c0-system, thus allowing for the relatively facile HAT reaction. The lowest kH value was measured for the reaction of N,N-diisobutylacetamide, wherein the steric bulk associated with the N-isobutyl groups increases the energy barrier required to reach the most suitable conformation for HAT. The experimental results are well supported by the computed BDEs for the C-H bonds of the most representative substrates.Peer reviewed: YesNRC publication: Ye