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ACE2 over‐expression regulates oxidative stress gene expression in the brainstem
Author(s) -
Xu Ping,
Lazartigues Eric
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1036.7
Subject(s) - nox4 , nox1 , nadph oxidase , oxidative stress , reactive oxygen species , angiotensin converting enzyme 2 , chemistry , microbiology and biotechnology , activator (genetics) , angiotensin ii , biochemistry , endocrinology , medicine , biology , gene , receptor , disease , covid-19 , infectious disease (medical specialty)
Angiotensin (Ang) I converting enzyme type 2 (ACE2) cleaves Ang II into the vasodilator Ang‐(1–7). We previously reported that ACE2 is expressed in the brain and involved in the prevention of hypertension via regulation of autonomic function. We also showed that ACE2 KO mice have increased levels of reactive oxygen species (ROS) in the brain. To clarify the role of ACE2 in the regulation of ROS levels, we performed an oxidative stress PCR array using brainstems from SA mice, with brain‐specific ACE2 overexpression, and control littermates (NT). In SA mice, the main ROS‐producing enzyme, NADPH oxidase, subunits genes Nox1 (gp91 phox homolog), Nox4, p22 phox and p67 phox were downregulated by −3.1, −1.6, −13.4 and −11 folds respectively, compared to controls. The NADPH oxidase activator 1 (Noxa1) and the dual oxidase1 (Duox1), which generates hydrogen peroxide, were also decreased by −2.6 and −1 fold, respectively. Anti oxidant stress enzymes like glutathione peroxidase 1, 3, 6, 8 subunits were downregulated by −180, −3, −2.4, −3.1 folds and so were SOD 1 (−1.2 fold) and 3 (−1.8 fold). Moreover, there was a trend to a reduction in lipid peroxidation (Tbars assay) in the brainstem of SA mice. These data show that ACE2 is regulating the expression of multiple genes involved in the formation and removal of ROS in the brainstem, which may contribute to the prevention of hypertension in this model. NIH RR018766 and HL093178