Abstract 070: Canonical Wnt Signaling Mediates Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility in Diabetic Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
En Yin Lai ◽  
Suping Zhang ◽  
Qian Huang ◽  
Qiaoling Wang ◽  
Liang Zhao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Wnt Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Diabetic Mice ◽  
Canonical Wnt Signaling ◽  
Protein Expressions ◽  
Afferent Arterioles ◽  
Gsk 3Β ◽  
Canonical Wnt

Background: Canonical Wnt signaling is involved in oxidative stress and diabetes but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to endothelin-1 (ET-1). Methods: Diabetic or control C57Bl/6 mice received vehicle or sulindac (40 mg·kg -1 ·day -1 ) to block canonical Wnt signaling for 4 weeks. ET-1 contractions were measured in diameter changes and H 2 O 2 and O 2 .- by fluorescence microscopy. Arteriolar protein expression and enzymatic activity were examined by standard methods. Results: Compared to control, diabetic mouse afferent arteriole had significantly increased O 2 .- (+84%) and H 2 O 2 (+91%) and enhanced sensitivity to ET-1 at 10 -8 mol·l -1 (-72±4% versus -43±4%, P<0.05) accompanied by significantly (P<0.005) reduced protein expressions and activities for catalase and superoxide dismutase 2 (SOD2). Incubation of afferent arterioles from normal or diabetic mice with PEG-SOD reduced responses to ET-1 whereas incubation with PEG-catalase reduced sensitivity to ET-1 selectively in arterioles from diabetic mice. The arteriolar protein expressions for canonical Wnt signaling indicated overactivation of this pathway in diabetic mice (2.6-fold increase in p-GSK-3β/GSK-3β and 3.3-fold decrease in p-β-catenin/β-catenin). Sulindac given to diabetic mice normalized the canonical Wnt signaling protein and arteriolar O 2 .- , H 2 O 2 and ET-1 contractions while doubling (P<0.05) microvascular catalase and SOD2. Conclusions: Increased ROS, notably H 2 O 2 , mediated by canonical Wnt signaling contributes to enhanced afferent arteriolar sensitivity to ET-1 in diabetes. Thus, antioxidant pharmacological strategies targeting canonical Wnt signaling may improve vascular function in diabetic nephropathy.

Copper inhibits hatching of fish embryos via inducing reactive oxygen species and down-regulating Wnt signaling

2018 ◽  
Vol 205 ◽  
pp. 156-164 ◽  
Author(s):  
YanJun Zhang ◽  
RuiTao Zhang ◽  
HaoJie Sun ◽  
Qi Chen ◽  
XueDong Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Wnt Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Fish Embryos

scholarly journals Activation of Wnt signaling by reactive oxygen species

2011 ◽  
Vol 356 (1) ◽  
pp. 134
Author(s):  
Jason Hwang ◽  
Jason Wen ◽  
Gregory Kelly
Keyword(s):  
Reactive Oxygen Species ◽  
Wnt Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals High Salt Enhances Reactive Oxygen Species and Angiotensin II Contractions of Glomerular Afferent Arterioles From Mice With Reduced Renal Mass

Hypertension ◽  
2018 ◽  
Vol 72 (5) ◽  
pp. 1208-1216 ◽  
Author(s):  
Lingli Li ◽  
En Yin Lai ◽  
Zaiming Luo ◽  
Glenn Solis ◽  
Margarida Mendonca ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Renal Mass ◽  
Reactive Oxygen ◽  
High Salt ◽  
Oxygen Species ◽  
Afferent Arterioles

5-AIQ inhibits H2O2-induced apoptosis through reactive oxygen species scavenging and Akt/GSK-3β signaling pathway in H9c2 cardiomyocytes

2013 ◽  
Vol 268 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Eun-Seok Park ◽  
Jun Chul Kang ◽  
Do-Hyun Kang ◽  
Yong Chang Jang ◽  
Kyu Yang Yi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
H9c2 Cardiomyocytes ◽  
Gsk 3Β ◽  
Induced Apoptosis

scholarly journals A divergent canonical WNT-signaling pathway regulates microtubule dynamics

2004 ◽  
Vol 164 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Lorenza Ciani ◽  
Olga Krylova ◽  
Matthew J. Smalley ◽  
Trevor C. Dale ◽  
Patricia C. Salinas
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Glycogen Synthase ◽  
Wnt Signaling Pathway ◽  
Negative Regulator ◽  
Canonical Wnt Signaling ◽  
Microtubule Stability ◽  
Gsk 3Β ◽  
Canonical Wnt

Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In the canonical WNT pathway, the negative regulator Axin forms a complex with β-catenin and GSK-3β, resulting in β-catenin degradation. Inhibition of GSK-3β by DVL increases β-catenin stability and TCF transcriptional activation. Here, we show that Axin associates with microtubules and unexpectedly stabilizes microtubules through DVL. In turn, DVL stabilizes microtubules by inhibiting GSK-3β through a transcription- and β-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3β–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3β, resulting in local changes in the phosphorylation of cellular targets. Our data indicate a bifurcation in the so-called canonical WNT-signaling pathway to regulate microtubule stability.

The inhibition of GSK-3β promotes the production of reactive oxygen species via β-catenin/C/EBPα signaling in the spleen of zebrafish (Danio rerio)

2018 ◽  
Vol 76 ◽  
pp. 110-120 ◽  
Author(s):  
Dongwu Liu ◽  
Hairui Yu ◽  
Lili Gao ◽  
Ao Li ◽  
Hongkuan Deng ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Danio Rerio ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Gsk 3Β
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