Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation.

By Xue-liang Du, D. Edelstein, L. Rossetti, I. Fantus, H. Goldberg, F. Ziyadeh, Jie Wu, M. Brownlee. Proceedings of the National Academy of Sciences of the United States of America, 2000

1,172 citations recorded by the source corpus.

Subfields: Clinical Biochemistry, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/6633063e68ce7f0d75b971a89b1746c3a9aed889

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Clinical Biochemistry

1. M. Brownlee
2. C. Palmeira
3. Stefanie Dimmeler
4. I. Goldfine
5. A. Rolo
6. B. Maddux
7. Joseph L. Evans
8. G. Grodsky

In Molecular Biology

1. M. Brownlee
2. J. Forbes
3. C. Palmeira
4. Qingzheng Kang
5. Stefanie Dimmeler
6. M. Cooper
7. A. Shah
8. Chunxue Yang

In Pathology and Forensic Medicine

1. M. Brownlee
2. Guy C. Brown
3. Chris E. Cooper

Citations in the corpus

• The pathobiology of diabetic complications: a unifying mechanism. (2005, background): “We began by asking the following question: What processes are increased by intracellular hyperglycemia in cells whose glucose transport rate is not downregulated by hyperglycemia but not increased in cells whose glucose transport rate is downregulated by hyperglycemia? We discovered that a consisten”
• Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. (2004, background): “For example, hyperglycemia induces mitochondrial O2 production, which has been shown to contribute to the activation of the hexosamine pathway and be involved in the pathogenesis of diabetic complications (31).”
• Hyperglycemia-induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway. (2002, background): “A direct correlation of hyperglycemia and oxidative stress in diabetic injuries, in particular mitochondrial damage, has been shown (29,36,38,41).”
• Mitochondrial dysfunction and molecular pathways of disease. (2007, background): “As a medical concern, hyperglycemia induces mitochondrial superoxide production by endothelial cells, which is an important mediator of diabetic complications such as cardiovascular disease (Green et al., 2004; Du et al., 2000).”
• Diabetes associated cell stress and dysfunction: role of mitochondrial and non‐mitochondrial ROS production and activity (2007, background): “Journal compilation C© 2007 The Physiological Society inhibits glyceraldehyde-3-phosphate dehydrogenase activity (Du et al. 2000), and activates the pathways related to hyperglycaemia-induced damage by diverting glycolytic metabolites to hexosamine synthesis.”
• Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. (2001, methodology): “Four major biochemical pathways of hyperglycemic vascular damage and hyperglycemia-induced activation of NF-κB have recently been shown to result from a single common mechanism: hyperglycemia-induced overproduction of superoxide by mitochondria (11, 12).”
• Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. (2003, methodology): “As described previously (6), the inhibitory effect of incubation in 30 mM glucose was completely prevented by overexpression of either UCP-1 (Figure 3b, bar 4) or MnSOD (Figure 3 b, bar 5), in parallel with the changes in poly(ADP-ribosyl)ation of GAPDH.”
• Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections (2023, background): “In turn, ROS induce TGFβ expression, contributing to the vicious self-stimulatory cycle between oxidative stress and hyperglycemia [85].”
• Mechanisms of diabetic complications. (2013, background): “These resulting sugar residues can compete with phosphate groups altering gene expression in diabetic tissues (162, 306, 520).”
• Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003, background): “This superoxide partially inhibits the glycolytic enzyme glyceraldehyde phosphate dehydrogenase (GAPDH), thereby diverting upstream metabolites from glycolysis into the four major glucose-driven signaling pathways that cause hyperglycemic damag”