Faculty Collaboration Database

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging. Am J Physiol Renal Physiol 2015 Aug 15;309(4):F377-82

Date

06/13/2015

Pubmed ID

26062875

Pubmed Central ID

PMC4596732

DOI

10.1152/ajprenal.00098.2015

Scopus ID

2-s2.0-84939495664 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat.

Author List

Salehpour F, Ghanian Z, Yang C, Zheleznova NN, Kurth T, Dash RK, Cowley AW Jr, Ranji M

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Flavin-Adenine Dinucleotide
Frozen Sections
Genotype
Hypertension
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
Kidney
Male
Microscopy, Fluorescence
Mitochondria
NAD
Oxidation-Reduction
Oxidative Stress
Phenotype
Phosphoproteins
Rats, Inbred Dahl
Rats, Transgenic
Sodium Chloride, Dietary
Time Factors