NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.

Nox2 oxidase is one isoform in a family of seven NADPH oxidases that generate reactive oxygen species (ROS) and thereby contribute to physiological and pathological processes including host defense, redox signaling and oxidative tissue damage. While alternative mRNA splicing has been shown to influe...

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Autores principales:	Craig B Harrison, Stavros Selemidis, Elizabeth Guida, Paul T King, Christopher G Sobey, Grant R Drummond
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/278954c7322b45f9a40040c6bac0f947
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spelling	oai:doaj.org-article:278954c7322b45f9a40040c6bac0f9472021-11-18T08:10:26ZNOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.1932-620310.1371/journal.pone.0048326https://doaj.org/article/278954c7322b45f9a40040c6bac0f9472012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23118986/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nox2 oxidase is one isoform in a family of seven NADPH oxidases that generate reactive oxygen species (ROS) and thereby contribute to physiological and pathological processes including host defense, redox signaling and oxidative tissue damage. While alternative mRNA splicing has been shown to influence the activity of several Nox-family proteins, functionally relevant splice variants of Nox2 have not previously been identified. We immunoscreened several mouse tissues and cells for the presence of truncated Nox2 proteins and identified a 30 kDa protein in lung, spleen and macrophages. RT-PCR analysis of mRNA from primary and immortalised (RAW264.7) mouse macrophages, and from human alveolar macrophages, identified a truncated Nox2 transcript which, upon sequence analysis, was found to be a product of the 'exon skipping' mode of alternative splicing, lacking exons 4-10 of the Nox2 gene. The predicted protein is comparable in size to that identified by immunoscreening and contains two transmembrane helices and an extended cytosolic C-terminus with binding sites for NADPH and the Nox organiser protein p47phox. Importantly, selective siRNA-mediated knockdown of the transcript reduced expression of the 30 kDa protein in macrophages, and suppressed phorbol ester-stimulated ROS production by 50%. We thus provide the first evidence that Nox2 undergoes alternative mRNA splicing to yield a 30 kDa protein - herein termed Nox2β - that regulates NADPH oxidase activity in macrophages from mice and humans. The discovery of Nox2β paves the way for future examination of its role in physiological and pathological processes.Craig B HarrisonStavros SelemidisElizabeth GuidaPaul T KingChristopher G SobeyGrant R DrummondPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48326 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Craig B Harrison Stavros Selemidis Elizabeth Guida Paul T King Christopher G Sobey Grant R Drummond NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
description	Nox2 oxidase is one isoform in a family of seven NADPH oxidases that generate reactive oxygen species (ROS) and thereby contribute to physiological and pathological processes including host defense, redox signaling and oxidative tissue damage. While alternative mRNA splicing has been shown to influence the activity of several Nox-family proteins, functionally relevant splice variants of Nox2 have not previously been identified. We immunoscreened several mouse tissues and cells for the presence of truncated Nox2 proteins and identified a 30 kDa protein in lung, spleen and macrophages. RT-PCR analysis of mRNA from primary and immortalised (RAW264.7) mouse macrophages, and from human alveolar macrophages, identified a truncated Nox2 transcript which, upon sequence analysis, was found to be a product of the 'exon skipping' mode of alternative splicing, lacking exons 4-10 of the Nox2 gene. The predicted protein is comparable in size to that identified by immunoscreening and contains two transmembrane helices and an extended cytosolic C-terminus with binding sites for NADPH and the Nox organiser protein p47phox. Importantly, selective siRNA-mediated knockdown of the transcript reduced expression of the 30 kDa protein in macrophages, and suppressed phorbol ester-stimulated ROS production by 50%. We thus provide the first evidence that Nox2 undergoes alternative mRNA splicing to yield a 30 kDa protein - herein termed Nox2β - that regulates NADPH oxidase activity in macrophages from mice and humans. The discovery of Nox2β paves the way for future examination of its role in physiological and pathological processes.
format	article
author	Craig B Harrison Stavros Selemidis Elizabeth Guida Paul T King Christopher G Sobey Grant R Drummond
author_facet	Craig B Harrison Stavros Selemidis Elizabeth Guida Paul T King Christopher G Sobey Grant R Drummond
author_sort	Craig B Harrison
title	NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
title_short	NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
title_full	NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
title_fullStr	NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
title_full_unstemmed	NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
title_sort	nox2β: a novel splice variant of nox2 that regulates nadph oxidase activity in macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/278954c7322b45f9a40040c6bac0f947
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NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.

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