Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats.
Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats.
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DOI：
10.3390/antiox11050927
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发表时间：
2022-05-09
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影响因子：
--
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中科院分区：
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II型糖尿病的发病增加了心脏对氧化损伤的易感性，因为相关的炎症和抗氧化反应减弱。转录因子NF-κB启动炎症，而NRF2控制抗氧化防御。目前的证据表明，在2型糖尿病(T2 DM)的表现中，这些转录因子之间的串扰可能会变得失调。这项研究的目的是检测转录因子和靶基因在T2 DM心脏进展过程中的动态变化。新的UC Davis T2 DM(UCD-T2 DM)大鼠分为：(1)瘦的对照组SD(n=7)，(2)胰岛素抵抗的糖尿病前期UCD-T2 DM(Pre；n=9)，(3)最近2周的糖尿病UCD-T2 DM(2wk；n=9)，(4)3个月糖尿病UCD-T2 DM(3Mo；n=14)，(5)6个月糖尿病UCD-T2 DM(6Mo；n=9)。3Mo和6Mo糖尿病大鼠的NF-κB乙酰化水平是SD大鼠和Pre大鼠的2倍。与SD相比，6Mo使NOX4蛋白增加了4倍。与SD组相比，Pre组NRF2易位增加82%，而6Mo组NRF2易位减少47%。与前相比，6Mo组的GCLM蛋白下降了35%。与SD组相比，6Mo组Hmox1基因表达降低45%。这些数据表明，在T2 DM的进展过程中，NF-κB相关基因增加，而NRF2基因被抑制或改变，从而使炎症持续存在，并降低了处理氧化负担的能力，从而改变了心脏的氧化还原状态。总体而言，这些变化可能会导致糖尿病相关的心血管并发症。
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.
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影响因子：
16.2
作者：
Laakso M
通讯作者：
Laakso M
DOI：
10.1073/pnas.1002178107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Kuroda, Junya;Ago, Tetsuro;Sadoshima, Junichi
通讯作者：
Sadoshima, Junichi
影响因子：
10.6
作者：
Franklin, Christopher C.;Backos, Donald S.;Mohar, Isaac;White, Collin C.;Forman, Henry J.;Kavanagh, Terrance J.
通讯作者：
Kavanagh, Terrance J.
影响因子：
10.5
作者：
Jaramillo MC;Zhang DD
通讯作者：
Zhang DD
影响因子：
8
作者：
Chowdhry, S.;Zhang, Y.;McMahon, M.;Sutherland, C.;Cuadrado, A.;Hayes, J. D.
通讯作者：
Hayes, J. D.