Evidence map›Paper›PMID 39902374›Full record

ArticleFrontiers in molecular biosciences2024

Alpha 1-antitrypsin mitigates salt-sensitive hypertension in juvenile mice by reducing diacylglycerol concentrations and protein kinase C activity in kidney membranes.

Yunus E Dogan, Niharika Bala, Erika S Galban, Russell L Lewis, Nancy D Denslow, Sihong Song, Abdel A Alli

Abstract read
In one paragraph

Article in Frontiers in molecular biosciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Yunus E DoganDepartment of Medicine Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL, United States.
Niharika BalaDepartment of Medicine Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL, United States.
Erika S GalbanDepartment of Medicine Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL, United States.
Russell L LewisDepartment of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida College of Veterinary Medicine, Gainesville, FL, United States.
Nancy D DenslowDepartment of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida College of Veterinary Medicine, Gainesville, FL, United States.
Sihong SongDepartment of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL, United States.
Abdel A AlliDepartment of Medicine Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL, United States.

Funding

The circadian clock protein BMAL and post-translational regulation of ENaC in the kidneyR01DK123078 · NIDDK · UNIVERSITY OF FLORIDA · PI ALLI, ABDEL AYUBE · 2020 to 2024
$1.7M
Applied Biosystems SCIEX Q-TRAP 6500 LC/MS/MS Mass SpectrometerS10OD018141 · OD · UNIVERSITY OF FLORIDA · PI DENSLOW, NANCY D · 2015 to 2015
$584k
NIDDK NIH HHS R01 DK123078NIH HHS S10 OD018141
6 · The paper itself

Abstract

Introduction: Recombinant alpha-1 antitrypsin (AAT) therapy has been shown to have beneficial effects to mitigate the progression of various diseases. Here, we hypothesized that administration of pharmaceutical-grade human AAT (hAAT) is effective in mitigating hypertension induced by salt-loading in juvenile mice by reducing the concentration of diacylglycerols (DAGs) and activity of protein kinase C (PKC) in the kidney. Methods: Four-week old 129Sv mice were salt-loaded to induce hypertension and then administered hAAT or vehicle. Results: Administration of hAAT was found to significantly reduce high blood pressure in both the active and inactive cycles of the 129Sv hypertensive mice. A lipidomic analysis showed decreased concentrations of multiple diacylglycerols in kidney cortex membrane fractions from mice treated with hAAT compared to vehicle. PKC activity was less in the 129Sv mice that received hAAT compared to vehicle. Western blotting and immunohistochemistry analysis showed the density of the sodium-potassium-chloride co-transporter (NKCC2) was significantly reduced in kidney cortex membrane fractions of juvenile mice that received hAAT compared to vehicle. Conclusion: Taken together, this study demonstrates a new protective effect of hAAT in normalizing blood pressure after the development of saltinduced hypertension in juvenile mice in a mechanism involving a decrease in NKCC2 membrane expression, presumably due to decreased levels of DAGs in the plasma membrane and a subsequent decrease in PKC activity.

Indexed as

alpha-1 antitrypsindiacylglycerolsprotein kinase Csalt-sensitive hypertensionsodium-potassium-chloride co-transporter

Identifiers

PMID39902374
PMCPMC11788078

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