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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Lipids, Membranes and Membranous Organelles
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1485506
This article is part of the Research Topic Protein Regulation by Lipids View all 3 articles

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

Provisionally accepted
Yunus E Dogan Yunus E Dogan Niharika Bala Niharika Bala Erika S Galban Erika S Galban Russell L Lewis Russell L Lewis Nancy Denslow Nancy Denslow Sihong Song Sihong Song Abdel A Alli Abdel A Alli *
  • University of Florida, Gainesville, Florida, United States

The final, formatted version of the article will be published soon.

    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. Four-week old 129Sv mice were salt-loaded to induce hypertension and then administered hAAT or vehicle. 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 sodiumpotassium-chloride co-transporter (NKCC2) was significantly reduced in kidney cortex membrane fractions of juvenile mice that received hAAT compared to vehicle. Taken together, this study demonstrates a new protective effect of hAAT in normalizing blood pressure after the development of salt-induced 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.

    Keywords: Protein Kinase C, Diacylglycerols, alpha-1 antitrypsin, Salt-sensitive hypertension, the sodium-potassium-chloride co-transporter

    Received: 23 Aug 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Dogan, Bala, Galban, Lewis, Denslow, Song and Alli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Abdel A Alli, University of Florida, Gainesville, 32609, Florida, United States

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