RGD Reference Report - NOX1/NADPH oxidase is involved in endotoxin-induced cardiomyocyte apoptosis. - Rat Genome Database

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NOX1/NADPH oxidase is involved in endotoxin-induced cardiomyocyte apoptosis.

Authors: Matsuno, Kuniharu  Iwata, Kazumi  Matsumoto, Misaki  Katsuyama, Masato  Cui, Wenhao  Murata, Ayumi  Nakamura, Hideo  Ibi, Masakazu  Ikami, Kanako  Zhang, Jia  Matoba, Satoaki  Jin, Denan  Takai, Shinji  Matsubara, Hiroaki  Matsuda, Naoyuki  Yabe-Nishimura, Chihiro 
Citation: Matsuno K, etal., Free Radic Biol Med. 2012 Nov 1;53(9):1718-28. doi: 10.1016/j.freeradbiomed.2012.08.590. Epub 2012 Sep 4.
RGD ID: 329955362
Pubmed: PMID:22982050   (View Abstract at PubMed)
DOI: DOI:10.1016/j.freeradbiomed.2012.08.590   (Journal Full-text)

The functional significance of NOX1/NADPH oxidase in the heart has not been explored due to its low expression relative to other NOX homologs identified so far. We aimed to clarify the role of NOX1/NADPH oxidase in the septic heart by utilizing mice deficient in the Nox1 gene (Nox1(-/Y)). Sepsis was induced by intraperitoneal administration of lipopolysaccharides (LPS: 25mg/kg) or cecal ligation and puncture (CLP) surgery. A marked elevation of NOX1 mRNA was demonstrated in cardiac tissue, which was accompanied by increased production of reactive oxygen species (ROS). In Nox1(-/Y) treated with LPS, cardiac dysfunction and survival were significantly improved compared with wild-type mice (Nox1(+/Y)) treated with LPS. Concomitantly, LPS-induced cardiomyocyte apoptosis and activation of caspase-3 were alleviated in Nox1(-/Y). The level of phosphorylated Akt in cardiac tissue was significantly lowered in Nox1(+/Y) but not in Nox1(-/Y) treated with LPS or that underwent CLP surgery. Increased oxidation of cysteine residues of Akt and enhanced interaction of Akt with protein phosphatase 2A (PP2A), a major phosphatase implicated in the dephosphorylation of Akt, were demonstrated in LPS-treated Nox1(+/Y). These responses to LPS were significantly attenuated in Nox1(-/Y). Taken together, ROS derived from NOX1/NADPH oxidase play a pivotal role in endotoxin-induced cardiomyocyte apoptosis by increasing oxidation of Akt and subsequent dephosphorylation by PP2A. Marked up-regulation of NOX1 may affect the risk of mortality under systemic inflammatory conditions.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NOX1HumanSepsis amelioratesISONox1 (Mus musculus) RGD 
Nox1RatSepsis amelioratesISONox1 (Mus musculus) RGD 
Nox1MouseSepsis amelioratesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nox1  (NADPH oxidase 1)

Genes (Mus musculus)
Nox1  (NADPH oxidase 1)

Genes (Homo sapiens)
NOX1  (NADPH oxidase 1)


Additional Information