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Salt‐Induced Oxidant Stress in Sprague‐Dawley (S‐D) Rats with a Deletion Mutation of the Nrf2 Gene
Author(s) -
Lombard Julian,
Kautenberg Katie,
Priestley Jessica,
Weinberg Brian,
Casati Marc,
Endres Bradley,
Geurts Aron
Publication year - 2015
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.29.1_supplement.795.5
Subject(s) - sod2 , catalase , superoxide dismutase , endocrinology , medicine , chemistry , oxidative stress , reactive oxygen species , glutathione reductase , wild type , mutant , heme oxygenase , microbiology and biotechnology , biology , heme , enzyme , biochemistry , gene , glutathione peroxidase
This study assessed the role of the master antioxidant and cell protective transcription factor nuclear factor (erythroid‐derived 2)‐like‐2 (NRF2) in mutant rats having a 41 base pair deletion in the first exon of the Nrf2 gene including the start codon for NRF2. The deletion was produced using TALEN technology and verified by PCR and immunohistochemistry. Expression of mRNA for the NRF2‐regulated indicator enzymes catalase, heme oxygenase‐1 (HO‐1), manganese superoxide dismutase (SOD2), and glutathione reductase (GSR) was significantly lower in livers of Nrf2 mutant rats fed high salt (HS; 4% NaCl) diet for 2 weeks vs. wild type controls. Acetylcholine (ACh)‐induced dilation of middle cerebral arteries (MCA) was similar in Nrf2 mutant rats and wild type controls fed low salt (0.4% NaCl) diet and eliminated by short term (3 days) HS diet in both strains. Low dose angiotensin II (ANG II) infusion (100 ng/kg/min, s.c.) restored ACh‐induced dilation in MCA of HS‐fed wild type rats but not in MCA of HS‐fed Nrf2 mutantrats. In S‐D rats fed HS diet, ANG II infusion increased NRF2/KEAP1 ratio and prevented the down regulation of mRNA for catalase, SOD2, HO‐1, and GSR. These results indicate that downregulation of the NRF2 system by salt‐induced ANG II suppression plays an important role in the vascular dysfunction associated with HS diet. [NIH #2R1R21OD018309‐01 and #2R56HL065289‐13].