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Article

Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity

1
Department of Physiology and Aging, University of Florida College of Medicine, Gainesville, FL 32610, USA
2
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida College of Veterinary Medicine, Gainesville, FL 32610, USA
3
Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2023, 11(5), 1489; https://doi.org/10.3390/biomedicines11051489
Submission received: 28 February 2023 / Revised: 28 April 2023 / Accepted: 12 May 2023 / Published: 20 May 2023

Abstract

Cathpesin B is a multi-functional protease that plays numerous roles in physiology and pathophysiology. We hypothesized that actin cytoskeleton proteins that are substrates of cathepsin B, various lipids, and kinases that are regulated by lipids would be down-regulated in the kidney of cathepsin B knockout mice. Here, we show by Western blot and densitometric analysis that the expression and proteolysis of the actin cytoskeleton proteins myristoylated alanine-rich C-kinase substrate (MARCKS) and spectrin are significantly reduced in kidney cortex membrane fractions of cathepsin B knockout mice compared to C57B6 wild-type control mice. Lipidomic results show that specific lipids are increased while other lipids, including lysophosphatidylcholine (LPC) species LPC (16:0), LPC (18:0), LPC (18:1), and LPC (18:2), are significantly decreased in membrane fractions of the kidney cortex from Cathepsin B null mice. Protein Kinase C (PKC) activity is significantly lower in the kidney cortex of cathepsin B knockout mice compared to wild-type mice, while calcium/calmodulin-dependent protein kinase II (CaMKII) activity and phospholipase D (PLD) activity are comparable between the two groups. Together, these results provide the first evidence of altered actin cytoskeleton organization, membrane lipid composition, and PKC activity in the kidneys of mice lacking cathepsin B.
Keywords: MARCKS; cathepsin B; lipids; protein kinase C MARCKS; cathepsin B; lipids; protein kinase C

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MDPI and ACS Style

Kawakibi, T.; Bala, N.; Liu, L.P.; Searcy, L.A.; Denslow, N.D.; Alli, A.A. Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity. Biomedicines 2023, 11, 1489. https://doi.org/10.3390/biomedicines11051489

AMA Style

Kawakibi T, Bala N, Liu LP, Searcy LA, Denslow ND, Alli AA. Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity. Biomedicines. 2023; 11(5):1489. https://doi.org/10.3390/biomedicines11051489

Chicago/Turabian Style

Kawakibi, Tamim, Niharika Bala, Lauren P. Liu, Louis A. Searcy, Nancy D. Denslow, and Abdel A. Alli. 2023. "Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity" Biomedicines 11, no. 5: 1489. https://doi.org/10.3390/biomedicines11051489

APA Style

Kawakibi, T., Bala, N., Liu, L. P., Searcy, L. A., Denslow, N. D., & Alli, A. A. (2023). Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity. Biomedicines, 11(5), 1489. https://doi.org/10.3390/biomedicines11051489

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