A reappraisal of the genomic organization of human Nox1 and its splice variants

被引:13
作者
Harper, RW [1 ]
Xu, CH
Soucek, K
Setiadi, H
Eiserich, JP
机构
[1] Univ Calif Davis, Sch Med, Dept Internal Med, Div Pulm Crit Care Med, Davis, CA 95616 USA
[2] Univ Calif Davis, Sch Med, Dept Internal Med, Div Nephrol, Davis, CA 95616 USA
[3] Univ Calif Davis, Sch Med, Dept Physiol & Membrane Biol, Davis, CA 95616 USA
[4] Univ Calif Davis, Sch Med, Canc Res Ctr, Davis, CA 95616 USA
关键词
Nox1; splice variant; oxidant; PCR; genomic;
D O I
10.1016/j.abb.2004.12.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The recent discovery of non-phagocytic NAD(P)H oxidases belonging to the Nox family of enzymes sharing extensive homology to the leukocyte NAD(P)H oxidase has revolutionized our Understanding of oxidative signaling related to fundamental biological processes and disease states. One form of this enzyme, Nox1, is a growth factor-responsive enzyme that catalyzes formation of the reactive oxygen species superoxide (O-2(.-)) and hydrogen peroxide (H2O2). Its expression is linked to a number of biological responses including cellular proliferation, angiogenesis, and activation of cellular signaling pathways. Whereas early published studies have described three distinct isoforms of Nox I, the current body of literature fails to adequately recognize this notion. Also, functional differences between isoforms remain relatively unexplored. Herein, we report that expression of human Nox1 is restricted to two distinct isoforms derived from a single gene; that is, the full-length gene product and a shorter spliced variant which lacks one of the NAD(P)H binding domains. We have developed PCR primer sets that distinguish between the two forms of Nox1 in several human cell lines. We could not find evidence for expression of the shortest reported form of Nox1 (NOH-1S), Previously identified as a proton channel, and the absence of paired splice sites in the gene suggests that it represents a reverse transcriptase artifact. A survey of the scientific literature reveals that the majority of studies related to Nox1 do not utilize molecular strategies that would adequately discern between the two Nox1 variants. The current literature suggest the two identified isoforms of human Nox1 (which we have named Nox1-L and Nox1-S) may be functionally distinct. Future Studies related to Nox1 will benefit from establishing the identity of the Nox1 isoform expressed and the functions attributed to each variant. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:323 / 330
页数:8
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