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Hypochlorite-Induced Structural Modifications Enhance The Chaperone Activity Of Human Α2-Macroglobulin, Amy Wyatt, Janet Kumita, Richard W. Mifsud, Cherrie A. Gooden, Mark Wilson, Christopher M. Dobson

Faculty of Science, Medicine and Health - Papers: part A

Hypochlorite, an oxidant generated in vivo by the innate immune system, kills invading pathogens largely by inducing the misfolding of microbial proteins. Concomitantly, the nonspecific activity of hypochlorite also damages host proteins, and the accumulation of damaged (misfolded) proteins is implicated in the pathology of a variety of debilitating human disorders (e.g., Alzheimer's disease, atherosclerosis, and arthritis). It is well-known that cells respond to oxidative stress by up-regulating proteostasis machinery, but the direct activation of mammalian chaperones by hypochlorite has not, to our knowledge, been previously reported. In this study, we show that hypochlorite-induced modifications of human α2-macroglobulin (α2M) markedly …