The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process.
Lysyl hydroxylase (or procollagen-lysine 5-dioxygenase) is an oxygenase enzyme that catalyzes the hydroxylation of lysine to hydroxylysine.[1][2] This reaction is necessary to the formation and stabilization of collagen
The PLOD1 gene provides instructions for making an enzyme called lysyl hydroxylase 1. This enzyme modifies a particular amino acid called lysine, which is one of the building blocks used to make proteins. Specifically, lysyl hydroxylase 1 adds a single oxygen atom to a hydrogen atom to create a charged molecule called a hydroxyl group. Hydroxyl groups attach to some of the lysines in collagen-like proteins. Collagens are complex molecules that provide strength, support, and elasticity (the ability to stretch) to many body tissues.
The addition of hydroxyl groups is essential for collagen molecules to form stable interactions, called cross-links, with one another. Cross-links between these molecules allow collagen to form networks of strong, slender fibrils, which are an important part of the normal structure of connective tissue (the tissue that binds and supports the body's muscles, ligaments, organs, and skin).
Effects of minoxidil on cultured human skin fibroblasts.
Pinnell SR, Murad S.
Source
Department of Medicine, Duke University Medical Center, Durham, N.C.
Abstract
Two important findings related to the effect of minoxidil on human skin fibroblasts in culture are reviewed. Treatment of cells with minoxidil is associated with a specific loss of lysyl hydroxylase activity; this loss occurs gradually and is reversed by removing minoxidil from the culture medium. Experiments with inhibitors of protein and RNA synthesis reveal that minoxidil may inhibit the synthesis of lysyl hydroxylase by acting at the transcriptional level. Treatment of cells with minoxidil is also associated with inhibition of proliferation, without any sign of cytotoxicity. This effect of minoxidil is accompanied by inhibition of DNA synthesis. Since collagen is the major product of fibroblast activity and lysyl hydroxylase catalyzes a crucial reaction in collagen biosynthesis, the combined effects of minoxidil offer the potential for its use as an antifibrotic agent. Thus, minoxidil may prove to be beneficial in treating skin conditions associated with collagen accumulation.
Να δούμε πότε κανένας καραγκιόζης θα ασχοληθεί σοβαρά με το περιβάλλον γύρω από το θύλακα και όχι με τον ίδιο το θύλακα.
Εδώ ισχύει κυριολεκτικά ότι ασχολούνται με το δέντρο και χάνουν (ή προσπαθούν να κρύψουν) το δάσος.
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