Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

Hsieh, Tusty‐Jiuan; Fustier, Pierre; Wei, Chih‐Chang; Zhang, Shaoling; Filep, János G.; Tang, Shiow-Shiu; Ingelfinger, Julie R.; Fantus, I. George; Hamet, Pavel; Chan, John S.D.

doi:10.1677/joe.1.05871

Cited by 45 publications

(49 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Importantly, this model also revealed increased activity of catalase and decreased glutathione (GSH) levels, consistent with increased oxidative stress. Concomitant insulin administration to PTCs subject to high glucose was shown to suppress the angiotensinogen gene expression (126). Moreover, antisense to angiotensinogen in this model abrogated high glucose-induced expression of angiotensinogen and abrogation of oxidative stress.…”

Section: B Ros and The Glomerular Basement Membrane (Gbm)mentioning

confidence: 73%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

139

123

View full text Add to dashboard Cite

Section: B Ros and The Glomerular Basement Membrane (Gbm)mentioning

confidence: 73%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

139

123

View full text Add to dashboard Cite

“…8). The antioxidative effect of azaserine has been noted in cultured renal proximal tubular cells (17). Moreover, the results with resveratrol suggest that the inhibition of superoxide generation by resveratrol accounts for the inhibition of endothelial adhesion molecule expression stimulated by HG and TNF-␣.…”

Section: Discussionmentioning

confidence: 94%

The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Rajapakse¹,

Ming²,

Carvas³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Rajapakse AG, Ming XF, Carvas JM, Yang Z. The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects. Am J Physiol Heart Circ Physiol 296: H815-H822, 2009. First published January 9, 2009 doi:10.1152/ajpheart.00756.2008.-Hexosamine biosynthetic pathway (HBP) accounts for some cardiovascular adverse effects of hyperglycemia. We investigated whether the HBP inhibitor azaserine protects against hyperglycemia-induced endothelial damage dependently of HBP. Human endothelial cells isolated from umbilical veins were exposed either to a high (30.5 mmol/l) or low concentration of glucose (5.5 mmol/l) for 4 days, followed by a stimulation with TNF-␣ (1 ng/ml, 24 h). The blockade of the rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase inhibited HBP flux and oxidative stress (generation of superoxide and peroxynitrite) under the hyperglycemic condition and prevented the synergistic stimulation of VCAM-1 and ICAM-1 expression by hyperglycemia and TNF-␣. In the cells cultured under a low-glucose condition when no increased HBP flux occurred, azaserine enhanced the manganese-superoxide dismutase (MnSOD) protein level and also inhibited the oxidative stress and the expression of VCAM-1 and ICAM-1 in response to TNF-␣. Moreover, the polyphenol resveratrol inhibited the oxidative stress and adhesion molecule expression and did not decrease the HBP flux under the hyperglycemia condition. In addition, in isolated rat aortas exposed to hyperglycemic buffer for 5 h when no significant HBP flux occurred, azaserine upregulated the MnSOD protein level and prevented decreased endothelium-dependent relaxations to acetylcholine. In conclusion, hyperglycemia independently increases oxidative stress and HBP flux, amplifies endothelial inflammation, and impairs endothelial function mainly through oxidative stress and not the HBP pathway. Azaserine protects against hyperglycemic endothelial damage through its antioxidant effect independently of inhibiting HBP pathway. adhesion molecules; endothelium; glucose; O-linked acetylglusamine; superoxide DIABETES MELLITUS is highly associated with an increased risk of cardiovascular morbidity and mortality (10, 34). Chronic hyperglycemia causes glucotoxicity to vascular cells, particularly the endothelial cells, resulting in an increased incidence of cardiovascular events (7). Clinical and experimental studies provide compelling evidence showing that hyperglycemia is associated with impaired endothelium-dependent relaxations (7) and increased endothelial expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) (20, 31). The decreased endothelial nitric oxide (NO) synthase (eNOS) function and upregulation of the adhesion molecules enhance the adhesion of inflammatory cells onto the endothelium followed by a transmigration of the cells into the subendothelial space, a key early process in atherogenesis (15). Numerous proi...

show abstract

“…22,49,50 ROS that were generated in E18 kidney explant were normalized with protein concentration and expressed as relative light units per milligram of protein.…”

Section: Ros Generationmentioning

confidence: 99%

Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis

Zhang

Chen

Tran

et al. 2007

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal D-glucose (5 mM) or high D-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high D-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as D-mannitol, L-glucose, and 2-deoxy-Dglucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

show abstract

Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

Cited by 45 publications

References 65 publications

Redox Control of Renal Function and Hypertension

Redox Control of Renal Function and Hypertension

The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis

Contact Info

Product

Resources

About