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Antioxidants
Volume 11
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10.3390/antiox11050927
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Article

Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats

by
Max A. Thorwald
1,*,
Jose A. Godoy-Lugo
1,2,
Ruben Rodriguez
3,
Kimber L. Stanhope
4,
James L. Graham
4,
Peter J. Havel
4,
Henry Jay Forman
1,2 and
Rudy M. Ortiz
2
1
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90017, USA
2
Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA
3
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA
4
Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, University of California, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2022, 11(5), 927; https://doi.org/10.3390/antiox11050927
Submission received: 28 April 2022 / Accepted: 3 May 2022 / Published: 9 May 2022
(This article belongs to the Special Issue Oxidative Stress in Cardiac Disease)
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Abstract

The onset of type II diabetes increases the heart’s susceptibility to oxidative damage because of the associated inflammation and diminished antioxidant response. Transcription factor NF-κB initiates inflammation while Nrf2 controls antioxidant defense. Current evidence suggests crosstalk between these transcription factors that may become dysregulated during type II diabetes mellitus (T2DM) manifestation. The objective of this study was to examine the dynamic changes that occur in both transcription factors and target genes during the progression of T2DM in the heart. Novel UC Davis T2DM (UCD-T2DM) rats at the following states were utilized: (1) lean, control Sprague-Dawley (SD; n = 7), (2) insulin-resistant pre-diabetic UCD-T2DM (Pre; n = 9), (3) 2-week recently diabetic UCD-T2DM (2Wk; n = 9), (4) 3-month diabetic UCD-T2DM (3Mo; n = 14), and (5) 6-month diabetic UCD-T2DM (6Mo; n = 9). NF-κB acetylation increased 2-fold in 3Mo and 6Mo diabetic animals compared to SD and Pre animals. Nox4 protein increased 4-fold by 6Mo compared to SD. Nrf2 translocation increased 82% in Pre compared to SD but fell 47% in 6Mo animals. GCLM protein fell 35% in 6Mo animals compared to Pre. Hmox1 mRNA decreased 45% in 6Mo animals compared to SD. These data suggest that during the progression of T2DM, NF-κB related genes increase while Nrf2 genes are suppressed or unchanged, perpetuating inflammation and a lesser ability to handle an oxidant burden altering the heart’s redox state. Collectively, these changes likely contribute to the diabetes-associated cardiovascular complications.
Keywords: mitochondrial dysfunction; diabetes; inflammation; antioxidants; oxidative stress mitochondrial dysfunction; diabetes; inflammation; antioxidants; oxidative stress

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MDPI and ACS Style

Thorwald, M.A.; Godoy-Lugo, J.A.; Rodriguez, R.; Stanhope, K.L.; Graham, J.L.; Havel, P.J.; Forman, H.J.; Ortiz, R.M. Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats. Antioxidants 2022, 11, 927. https://doi.org/10.3390/antiox11050927

AMA Style

Thorwald MA, Godoy-Lugo JA, Rodriguez R, Stanhope KL, Graham JL, Havel PJ, Forman HJ, Ortiz RM. Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats. Antioxidants. 2022; 11(5):927. https://doi.org/10.3390/antiox11050927

Chicago/Turabian Style

Thorwald, Max A., Jose A. Godoy-Lugo, Ruben Rodriguez, Kimber L. Stanhope, James L. Graham, Peter J. Havel, Henry Jay Forman, and Rudy M. Ortiz. 2022. "Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats" Antioxidants 11, no. 5: 927. https://doi.org/10.3390/antiox11050927

APA Style

Thorwald, M. A., Godoy-Lugo, J. A., Rodriguez, R., Stanhope, K. L., Graham, J. L., Havel, P. J., Forman, H. J., & Ortiz, R. M. (2022). Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats. Antioxidants, 11(5), 927. https://doi.org/10.3390/antiox11050927

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