Aldose reductase in the BB rat: isolation, immunological identification and localization in the retina and peripheral nerve

Aldose reductase was purified from testis of nondiabetic BB rats using DEAE cellulose, hydroxylapatite and sephadex G-100 column chromatography. The molecular weight of the isolated enzyme was found to be 36,500±1000. Antibody against the isolated enzyme was raised in rabbits. It was purified by affinity chromatography, characterised by double immunodiffusion and Western blot analysis and used to localize the enzyme in retina and in peripheral nerve of the BB rat. In the retina, aldose reductase immunoreactivity was seen in the ganglion cells, Müller cell processes, retinal pigment epithelium and in the pericytes and endothelial cells of retinal capillaries. In peripheral nerve, aldose reductase immunoreactivity was found in the paranodal cytoplasm of Schwann cells and in pericytes and endothelial cells of endoneurial capillaries.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46019/1/125_2004_Article_BF00270423.pd

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference