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Redox Biol. 2018 Jun;16:248-254. doi: 10.1016/j.redox.2018.02.024. Epub 2018 Mar 6.

Lipid peroxidation regulates podocyte migration and cytoskeletal structure through redox sensitive RhoA signaling.

Author information

1
Oxidative Stress and Disease Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, 70808 LA, USA.
2
Immunogenetics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, 70808 LA, USA.
3
Islet Cell Biology Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, 70808 LA, USA.
4
Regulation of Gene Expression Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, 70808 LA, USA.
5
Oxidative Stress and Disease Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, 70808 LA, USA. Electronic address: krisztian.stadler@pbrc.edu.

Abstract

Early podocyte loss is characteristic of chronic kidney diseases (CKD) in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes. We found that lipid radicals govern changes in podocyte homeostasis through redox sensitive RhoA signaling: lipid radicals inhibit migration and cause loss of F-actin fibers. These effects were prevented by mutating the redox sensitive cysteines of RhoA. We therefore suggest that in diseases associated with increased lipid peroxidation, lipid radicals can determine podocyte function with potentially pathogenic consequences for kidney physiology.

KEYWORDS:

Chronic kidney disease; Cysteine; Lipid peroxidation; Podocyte; Reactive lipids; RhoA

PMID:
29547847
PMCID:
PMC5854917
DOI:
10.1016/j.redox.2018.02.024
[Indexed for MEDLINE]
Free PMC Article

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