Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin

Abstract Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tiss...

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Autores principales:	Vivek Gupta, Mehdi Mirzaei, Veer Bala Gupta, Nitin Chitranshi, Yogita Dheer, Roshana Vander Wall, Mojdeh Abbasi, Yuyi You, Roger Chung, Stuart Graham
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9b70b9ed1e54766a0cc9a682a0c7d4e
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spelling	oai:doaj.org-article:e9b70b9ed1e54766a0cc9a682a0c7d4e2021-12-02T12:32:37ZGlaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin10.1038/s41598-017-08688-22045-2322https://doaj.org/article/e9b70b9ed1e54766a0cc9a682a0c7d4e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08688-2https://doaj.org/toc/2045-2322Abstract Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tissues from control and glaucoma subjects as well as retinas from experimental glaucoma rats were analysed to establish changes in plasmin and neuroserpin activity. Neuroserpin undergoes oxidative inactivation in glaucoma which leads to augmentation of plasmin activity. Neuroserpin contains several methionine residues in addition to a conserved reactive site methionine and our study revealed enhanced oxidation of Met residues in the serpin under glaucoma conditions. Met oxidation was associated with loss of neuroserpin inhibitory activity and similar findings were observed in the retinas of superoxide dismutase (SOD) mutant mice that have increased oxidative stress. Treatment of purified neuroserpin with H2O2 further established that Met oxidation inversely correlated with its plasmin inhibitory activity. Dysregulation of the plasmin proteolytic system associated with increased degradation of the extracellular matrix (ECM) proteins in the retina. Collectively, these findings delineate a novel molecular basis of plasmin activation in glaucoma and potentially for other neuronal disorders with implications in disease associated ECM remodelling.Vivek GuptaMehdi MirzaeiVeer Bala GuptaNitin ChitranshiYogita DheerRoshana Vander WallMojdeh AbbasiYuyi YouRoger ChungStuart GrahamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vivek Gupta Mehdi Mirzaei Veer Bala Gupta Nitin Chitranshi Yogita Dheer Roshana Vander Wall Mojdeh Abbasi Yuyi You Roger Chung Stuart Graham Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
description	Abstract Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tissues from control and glaucoma subjects as well as retinas from experimental glaucoma rats were analysed to establish changes in plasmin and neuroserpin activity. Neuroserpin undergoes oxidative inactivation in glaucoma which leads to augmentation of plasmin activity. Neuroserpin contains several methionine residues in addition to a conserved reactive site methionine and our study revealed enhanced oxidation of Met residues in the serpin under glaucoma conditions. Met oxidation was associated with loss of neuroserpin inhibitory activity and similar findings were observed in the retinas of superoxide dismutase (SOD) mutant mice that have increased oxidative stress. Treatment of purified neuroserpin with H2O2 further established that Met oxidation inversely correlated with its plasmin inhibitory activity. Dysregulation of the plasmin proteolytic system associated with increased degradation of the extracellular matrix (ECM) proteins in the retina. Collectively, these findings delineate a novel molecular basis of plasmin activation in glaucoma and potentially for other neuronal disorders with implications in disease associated ECM remodelling.
format	article
author	Vivek Gupta Mehdi Mirzaei Veer Bala Gupta Nitin Chitranshi Yogita Dheer Roshana Vander Wall Mojdeh Abbasi Yuyi You Roger Chung Stuart Graham
author_facet	Vivek Gupta Mehdi Mirzaei Veer Bala Gupta Nitin Chitranshi Yogita Dheer Roshana Vander Wall Mojdeh Abbasi Yuyi You Roger Chung Stuart Graham
author_sort	Vivek Gupta
title	Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
title_short	Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
title_full	Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
title_fullStr	Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
title_full_unstemmed	Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
title_sort	glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e9b70b9ed1e54766a0cc9a682a0c7d4e
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Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin

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