The unfolded protein response in lens epithelial cells from galactosemic rat lenses.

Purpose: Diabetic complications are associated with hypoglycemia and hyperglycemia. The purpose of this study was to investigate the effect of both glucose deprivation and hyperglycemia on the induction of endoplasmic reticulum (ER) stress and the subsequent activation of the unfolded protein response (UPR) that results in apoptosis in in vitro cultured lens epithelial cells (LECs) and in vivo cataract formation in galactose-fed rats.

Methods: Lenses from rats fed a standard diet containing 50% galactose with or without an aldose reductase inhibitor (ARI) were investigated.

Platinum anticancer drug damage enforces a particular rotational setting of DNA in nucleosomes.

We constructed two site-specifically modified nucleosomes containing an intrastrand cis-{Pt(NH3)2}2+ 1,3-d(GpTpG) cross-link, similar to one formed by the anticancer drugs carboplatin and cisplatin on DNA, and investigated their structures by hydroxyl radical footprinting and exonuclease III digestion. Hydroxyl radical footprinting demonstrated that the presence of the platinum cross-link selects out a specific rotational setting of DNA on the histone octamer core in each of two reconstituted nucleosomes in which the platinum positions differ by half a DNA helical turn. The {Pt(NH3)2}2+ cross-link is situated in a structurally similar location, with the undamaged strand projecting outward, forcing the DNA to adopt opposite rotational settings in its wrapping around the histone octamer in the two nucleosomes.