Dr Bhave and lab members' publication published
July 21st 2017
Role of Hypohalous Acids in Basement Membrane Homeostasis.Colon S1, Page-McCaw P2, Bhave G3,4.
Basement membranes (BMs) are sheet-like structures of specialized extracellular matrix that underlie nearly all tissue cell layers including epithelial, endothelial, and muscle cells. BMs not only provide structural support, but are critical for the development, maintenance, and repair of organs. Animal heme peroxidases generate highly reactive hypohalous acids extracellularly and therefore target BMs for oxidative modification. Given the importance of BMs in tissue structure and function, hypohalous acid mediated oxidative modifications of BM proteins represent a key mechanism in normal development and pathogenesis of disease. Recent Advances: Peroxidasin, a BM associated animal heme peroxidase, generates hypobromous acid (HOBr) to form sulfilimine cross-links within the collagen IV network of BM. These cross-links stabilize BM and are critical for animal tissue development. These findings highlight a paradoxical anabolic role for HOBr, which typically damages protein structure leading to dysfunction.
The molecular mechanism whereby peroxidasin uses HOBr as a reactive intermediate to cross-link collagen IV, yet avoid collateral damage to nearby BM proteins remains unclear.
The exact identification and functional impact of specific hypohalous acid mediated modifications of BM proteins needs to be addressed to connect these modifications to tissue development and pathogenesis of disease. As seen with the sulfilimine cross-link of collagen IV, hypohalous acid oxidative events may be beneficial in select situations rather than uniformly deleterious.
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