ArticleAmerican journal of translational research2023
Tempol treatment normalizes membrane expression of epithelial transport proteins in the kidney of salt-loaded hypertensive diabetic db/db mice.
Article in American journal of translational research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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5 authors at 1 institution in 2 countries.
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Abstract
objectiveHypertension exacerbates the progression and severity of diabetic kidney disease. In this study, we addressed the hypothesis that tempol acts at multiple segments of the nephron to normalize the abundance of sodium coupled epithelial transport proteins in the luminal plasma membrane to mitigate high blood pressure in salt-loaded hypertensive diabetic db/db mice.
methodsSoluble and membrane fractions from freshly homogenized kidney cortex tissue samples were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and probed for specific proteins by Western blotting. Western blotting for specific urinary extracellular vesicle (uEV) markers and nanoparticle tracking analysis was performed to characterize each uEV preparation from each group. A one-way ANOVA was performed to determine statistical significance between three groups (hypertensive diabetic db/db mice treated with vehicle, hypertensive diabetic db/db mice treated with tempol, and wild-type mice).
resultsTempol treatment reduced systolic blood pressure in hypertensive diabetic db/db mice compared to db/db mice that received vehicle. We observed attenuated membrane protein expression of the sodium hydrogen exchanger 3 (NHE3), sodium potassium chloride co-transporter (NKCC2), sodium chloride cotransporter (NCC), and epithelial sodium channel (ENaC) in the kidney of salt-loaded hypertensive diabetic db/db mice infused with tempol by osmotic minipump for 5 days compared to hypertensive diabetic db/db mice infused with vehicle. Also, the infusion of tempol in hypertensive diabetic db/db mice reduced the augmented protein expression of protein kinase c (PKC) epsilon observed in the vehicle treated hypertensive diabetic db/db kidney when compared to the healthy wild-type kidney. The amount of uEV and their size profiles were comparable between the three groups.
conclusionsThis study demonstrates that tempol down-regulates epithelial transport mechanisms in each segment of the nephron and normalizes salt-induced high blood pressure in diabetic animals presumably in a PKC dependent manner.
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Identifiers
38186979PMC10767517W4390689639What Socratic holds
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