Thioredoxin-related regulation of NO/NOS activities.
The role of regulation of nitric oxide synthase (NOS) activity in mitigating oxidative stress in neonatal lungs and contributing to pulmonary vasodilation at birth is still unclear. Furthermore, it is known that, depending on interactions between the individual components of the mitogen-activated protein kinase (MAPK) signaling cascades, many biological consequences, including apoptosis, are initiated. Although the importance of nitric oxide (NO) in apoptosis is controversial and likely depends on NO concentrations and cell types, this highly reactive free radical can activate the p38 MAPK signal cascade. Recent studies have suggested that thioredoxin may play an important role as an effector for some of these functions. Thioredoxin is a major redox protein for many enzymes/transcription factors and is involved in cellular functions, such as viability, activation, and proliferation. In addition to its redox regulation, thioredoxin binds directly to the apoptosis signal-regulating kinase 1 (ASK1), thus inhibiting the activation of stress-induced MAPK signaling cascades that lead to apoptosis. Furthermore, NO produced from newly induced neuronal NOS was reported to induce expression of thioredoxin and several other genes for preconditioning-induced neuroprotection. Moreover, although exposure of endothelial cells to NO decreases NOS activity, this inhibition was shown to be reversed by thioredoxin. Finally, the correlation of expression of thioredoxin with endothelial NOS activity seems to suggest an important role played by this protein in perinatal changes of pulmonary artery functions. Therefore, thioredoxin may participate in the regulation of NOS activity and be involved in NO functions via multiple mechanisms.
Shao
Li-En
LE
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Tanaka
Tetsuya
T
Gribi
Ruby
R
Yu
John
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D013879:Thioredoxins / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D009569:Nitric Oxide; D013879:Thioredoxins; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D020928:Mitogen-Activated Protein Kinases