Calcineurin A-α suppression drives nuclear factor-κB-mediated NADPH oxidase-2 upregulation

Author:

Cheriyan Aswathy M.1,Ume Adaku C.2ORCID,Francis Cynthia E.3,King Keyona N.1,Linck Valerie A.1,Bai Yun3,Cai Hui14,Hoover Robert S.14,Ma Heping P.1,Gooch Jennifer L.134,Williams Clintoria R.124

Affiliation:

1. Division of Nephrology, Department of Medicine, and Department of Physiology, Emory University, Atlanta, Georgia

2. Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, Ohio

3. Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, Georgia

4. Research Service, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia

Abstract

A long-term consequence of calcineurin inhibitors (CNIs) is oxidative damage and nephrotoxicity. This study indicates that NF-κB is a novel calcineurin-regulated transcription factor that is activated with calcineurin inhibition, thereby driving oxidative damage in CNI nephropathy. These findings provide additional evidence of divergent calcineurin signaling pathways and suggest that selective CNIs could improve the long-term outcomes of patients by mitigating renal side effects.

Funder

American Heart Association

HHS | National Institutes of Health

Publisher

American Physiological Society

Subject

Physiology

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