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Publication
Cardiac NF-?B Acetylation Increases While Nrf2-Related Gene Expression and
Mitochondrial Activity Are Impaired during the Progression of Diabetes in
UCD-T2DM Rats.
Authors Thorwald MA, Godoy-Lugo JA, Rodriguez R, Stanhope KL, Graham JL, Havel PJ,
Forman HJ, Ortiz RM
Submitted By Submitted Externally on 6/21/2022
Status Published
Journal Antioxidants (Basel, Switzerland)
Year 2022
Date Published 5/1/2022
Volume : Pages 11 : Not Specified
PubMed Reference 35624791
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-?B 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-?B 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-?B 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.




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