Purpose. The purpose of this study was to investigate the effect of curcumin and its source, turmeric, on streptozotocin-induced diabetic cataract in rats.

Mutations in elongation of very long-chain fatty acid-4 (ELOVL4) are associated with autosomal dominant Stargardt-like macular degeneration (STGD3), with a five base-pair (5 bp) deletion mutation resulting in the loss of 51 carboxy-terminal amino acids and truncation of the protein. In addition to the retina, Elovl4 is expressed in a limited number of mammalian tissues, including skin, with unknown function(s). We generated a knock-in mouse model with the 5-bp deletion in the Elovl4 gene. As anticipated, mice carrying this mutation in the heterozygous state (Elovl4^+/del) exhibit progressive photoreceptor degeneration. Unexpectedly, homozygous mice (Elovl4^del/del) display scaly, wrinkled skin, have severely compromised epidermal permeability barrier function, and die within a few hours after birth. Histopathological evaluation of the Elovl4^del/del pups revealed no apparent abnormality(ies) in vital internal organs. However, skin histology showed an abnormally-compacted outer epidermis [stratum corneum (SC)], while electron microscopy revealed deficient epidermal lamellar body contents, and lack of normal SC lamellar membranes that are essential for permeability barrier function. Lipid analyses of epidermis from Elovl4^del/del mice revealed a global decrease in very long-chain fatty acids (VLFAs) (i.e., carbon chain ≥C28) in both the ceramide/glucosylceramide and the free fatty-acid fractions. Strikingly, Elovl4^del/del skin was devoid of the epidermal-unique ω-O-acylceramides, that are key hydrophobic components of the extracellular lamellar membranes in mammalian SC. These findings demonstrate that ELOVL4 is required for generating VLFA critical for epidermal barrier function, and that the lack of epidermal ω-O-acylceramides is incompatible with survival in a desiccating environment.

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff’s base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.

The chaperone activity and biophysical properties of recombinant human alphaA- and alphaB-crystallins were studied by light scattering and spectroscopic methods. While the chaperone function of alphaA-crystallin markedly improves with an increase in temperature, the activity of alphaB homopolymer appears to change very little upon heating. Compared with alphaB-crystallin, the alphaA-homopolymer is markedly less active at low temperatures, but becomes a more active species at high temperatures. At physiologically relevant temperatures, the alphaB homopolymer appears to be modestly (two times or less) more potent chaperone than alphaA homopolymer. In contrast to very similar thermotropic changes in the secondary structure of both homopolymers, alphaA- and alphaB-crystallins markedly differ with respect to the temperature-dependent surface hydrophobicity profiles. Upon heating, alphaA-crystallin undergoes a conformational transition resulting in the exposure of additional hydrophobic sites, whereas no such transition occurs for alphaB-crystallin. The correlation between temperature-dependent changes in the chaperone activity and hydrophobicity properties of the individual homopolymers supports the view that the chaperone activity of alpha-crystallin is dependent on the presence of surface-exposed hydrophobic patches. However, the present data also show that the surface hydrophobicity is not the sole determinant of the chaperone function of alpha-crystallin.

α‐Crystallin, a prominent member of small heat shock protein (sHsp) family and a major structural protein of the eye lens is a large polydisperse oligomer of two isoforms, αA‐ and αB‐crystallins. Numerous studies have demonstrated that α‐crystallin functions like a molecular chaperone in preventing the aggregation of various proteins under a wide range of stress conditions. The molecular chaperone function of α‐crystallin is thus considered to be vital in the maintenance of lens transparency and in cataract prevention. α‐Crystallin selectively interacts with non‐native proteins thereby preventing them from aggregation and helps maintain them in a folding competent state. It has been proposed and generally accepted that α‐crystallin suppresses the aggregation of other proteins through the interaction between hydrophobic patches on its surface and exposed hydrophobic sites of partially unfolded substrate protein. However, a quantifiable relationship between hydrophobicity and chaperone‐like activity remains a matter to be concerned about. On an attentive review of studies on α‐crystallin chaperone‐like activity, particularly the studies that have direct or indirect implications to hydrophobicity and chaperone‐like activity, we found several instances wherein the correlation between hydrophobicity and its chaperone‐like activity is paradoxical. We thus attempted to provide an overview on the role of hydrophobicity in chaperone‐like activity of α‐crystallin, the kind of evaluation done for the first time. iubmb Life, 58: 632 ‐ 641, 2006