Signaling of Reactive Oxygen and Nitrogen Species in Diabetes Mellitus

Disorder of physiological signaling functions of reactive oxygen species(ROS) superoxide and hydrogen peroxide and reactive nitrogen species (RNS) nitric oxide and peroxynitrite is an important feature of diabetes mellitus type 1 and type 2. It is now known that hyperglycemic conditions of cells are associated with the enhanced levels of ROS mainly generated by mitochondria and NADPH oxidase. It has been established that ROS stimulate many enzymatic cascades under normal physiological conditions, but hyperglycemia causes ROS overproduction and the deregulation of ROS signaling pathways initiating the development of diabetes mellitus. On the other hand the deregulation of RNS signaling leads basically to a decrease in NO formation with subsequent damaging disorders. In the present work we will consider the pathological changes of ROS and RNS signaling in enzyme/gene regulated processes catalyzed by protein kinases C and B (Akt/B), phosphatidylinositol 3′-kinase (PI3-kinase), extracellular signal-regulated kinase 1/2 (ERK1/2) and some others. Furthermore we will discuss a particularly important role of several ROS-regulated genes and adapter proteins such as the p66shc, FOXO3a and Sirt2. The effects of low and high ROS levels in diabetes will be also considered. Thus the regulation of damaging ROS levels in diabetes by antioxidants and free radical scavengers must be one of promising treatment of this disease, however, because of the inability of traditionalantioxidative vitamin E and C to interact with superoxide and hydrogen peroxide,new free radical scavengers such as flavonoids, quinones and synthetic mimetics of superoxide dismutase (SOD) should be intensively studied.

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Strategy of Chemical Modification to Free Radical Scavengers for Suppression of Hydrogen Peroxide-Induced Cytotoxicity

Food Factors for Cancer Prevention ◽

10.1007/978-4-431-67017-9_127 ◽

1997 ◽

pp. 642-646 ◽

Cited By ~ 1

Author(s):

Tsutomu Nakayama

Keyword(s):

Hydrogen Peroxide ◽

Free Radical ◽

Chemical Modification ◽

Free Radical Scavengers ◽

Radical Scavengers

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Effect of Free Radical Scavengers and Metal Ion Chelators on Hydrogen Peroxide and Phenylhydrazine Induced Red Blood Cell Lipid Peroxidation

Free Radical Research Communications ◽

10.3109/10715768709069791 ◽

1987 ◽

Vol 3 (1-5) ◽

pp. 257-263 ◽

Cited By ~ 6

Author(s):

Hermann Einsele ◽

Michael R. Clemens ◽

Ulrike Wegner ◽

Hans-Dierck Waller

Keyword(s):

Hydrogen Peroxide ◽

Lipid Peroxidation ◽

Free Radical ◽

Blood Cell ◽

Red Blood Cell ◽

Metal Ion ◽

Free Radical Scavengers ◽

Radical Scavengers ◽

Cell Lipid ◽

Metal Ion Chelators

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Peroxide-cyclooxygenase interactions in postasphyxial changes in retinal and choroidal hemodynamics

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.6.2039 ◽

1995 ◽

Vol 78 (6) ◽

pp. 2039-2046 ◽

Cited By ~ 37

Author(s):

S. Chemtob ◽

P. Hardy ◽

D. Abran ◽

D. Y. Li ◽

K. Peri ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Free Radical ◽

Cumene Hydroperoxide ◽

Reactive Oxygen ◽

Free Radical Scavengers ◽

Cyclooxygenase Inhibitors ◽

High Dose ◽

Oxygen Species ◽

Radical Scavengers ◽

Thromboxane Synthase

To test the role of reactive oxygen species and cyclooxygenase products in the retinal hemodynamic changes induced by asphyxia, we measured retinal (RBF) and choroidal blood flows (ChBF), malondialdehyde (MDA), prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) in 1- to 3-day-old pigs treated with saline, the free radical scavengers U-74389F or high-dose allopurinol, the cyclooxygenase inhibitors ibuprofen or indomethacin, or the thromboxane synthase blocker CGS-13080 before and 5 and 60 min after a 5-min period of asphyxia. In saline-treated animals, RBF and ChBF increased 5 min after asphyxia and decreased at 60 min. The increases in RBF and ChBF at 5 min postasphyxia were slightly attenuated by cyclooxygenase blockers and free radical scavengers but not by thromboxane synthase inhibition, whereas all drugs prevented the decreases at 60 min. MDA, TxB2, PGE2, and 6-keto-PGF1 alpha increased 5 min after asphyxia; at 60 min, PGE2 and 6-keto-PGF1 alpha returned to nearly preasphyxial levels, but MDA and TxB2 continued to increase. Cyclooxygenase inhibition prevented the asphyxia-induced rise in MDA, and the free radical scavengers prevented that of prostanoids. In isolated eyecup preparations, H2O2 and cumene hydroperoxide constricted retinal arteries; this effect was blocked by cyclooxygenase and thromboxane synthase inhibitors. The data suggest that during oxidative stresses reactive oxygen species are generated from the cyclooxygenase pathway and, in turn, also activate the synthesis of thromboxane; the latter mediates the oxidative stress-induced ocular vasoconstriction that might trigger the neovascularization of retinopathy of prematurity.

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