Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage

By T. Nishikawa, D. Edelstein, Xue-liang Du, Sho-ichi Yamagishi, T. Matsumura, Y. Kaneda, M. Yorek, D. Beebe, P. Oates, H. Hammes and 2 more. Nature, 2000

4,496 citations recorded by the source corpus.

Subfields: Cell Biology, Clinical Biochemistry, Physiology

View Paper: https://www.semanticscholar.org/paper/8e05a1ce6103477137f939b939a6a2b52c12d005

How researchers see this paper

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

In Cell Biology

1. J. Forbes
2. M. Cooper
3. Antonio Ceriello
4. M. Yorek
5. R. Robertson
6. Toren Finkel
7. W. Sivitz

In Clinical Biochemistry

1. C. Palmeira
2. A. Rolo
3. M. Brownlee
4. George Perry
5. Stefanie Dimmeler
6. I. Goldfine
7. B. Maddux
8. W. Dröge

In Physiology

1. W. Sivitz
2. M. Yorek
3. M. Brownlee
4. Antonio Ceriello
5. J. Forbes
6. C. Palmeira
7. Qingzheng Kang
8. Nikki J. Holbrook

Citations in the corpus

• Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. (2004, background): “Indeed, recent studies by Brownlees's group suggest elevated levels of glucose that trigger these processes and indirectly cause increased intracellular generation of superoxide anion and other radicals.(12) This chapter specifically focuses on proposed mechanisms by which AGE accumulate in the extr”
• Free radicals in the physiological control of cell function. (2002, background): “In aorta endothelial cells, a pathologically relevant elevation of the extracellular glucose concentration was shown to cause a massive increase in ROS production by the mitochondrial ETC (415).”
• Essential fatty acids: biochemistry, physiology and pathology (2006, background): “This is supported by the observation that uncoupling decreases glucose-induced ROS formation, and thus prevents vascular damage in cultured endothelial cells [149].”
• Free radicals and antioxidants in normal physiological functions and human disease. (2007, background): “However, diabetes alters the primary sites of superoxide generation so that complex II becomes the primary source of electrons that contribute to superoxide formation under diabetic conditions (Nishikawa et al., 2000).”
• Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. (2018, background): “The NADPH oxidases (NOX), a family of seven membrane-bound enzyme complexes, catalyze the reduction of molecular oxygen to O2 ● by using NADPH as electron donor, thus producing ROS as their only function [1-3, 7, 37, 38], and this reflects their specific role in inducing a burst of ROS”
• Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production (2000, background): “Accordingly, it has been postulated that a mild uncoupling of respiration by UCPs could regulate ROS production by modulating proton leakage through the inner mitochondrial membran”
• Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. (2001, background): “Consistent with this concept, a recent study demonstrated that hyperglycemia-dependent overproduction of mitochondrial superoxide results in NF- B activation (16).”
• Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. (2005, background): “Polyol pathway-mediated alterations in pyridine nucleotides have been linked to diverse metabolic changes such as the synthesis of nitric oxide (NO) and activation of protein kinases (39).”
• Mechanisms of diabetic complications. (2013, background): “Superoxide (O2 ) generation by dysfunctional mitochondria in diabetes has been postulated as the primary initiating event in the development of diabetic complications (425).”
• Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part I (2003, background): “Indeed, hyperglycemia-induced ROS production triggers several cellularmechanisms includingpolyol andhexosamine flux, advancedglycation end products (AGEs), protein kinase C (PKC) activation, and NF-kB-mediated vascular inflammation.(12,13) One of the main sources of ROS in the setting of hyperglycem”
• Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. (2001, background): “Since hyperglycemia activates protein kinase C in BAECs by increasing mitochondrial superoxide production (11), inhibition of this vascular action of insulin in vivo by hyperglycemia could further enhance the difference in eNOS activity between diabetics and nondiabetics.”