Induction of vascular endothelial growth factor by nitric oxide in cultured human articular chondrocytes.
We investigated the role of nitric oxide (NO) in the control of vascular endothelial growth factor A (VEGF) gene expression in cultured human articular chondrocytes. Cell treatment with the NO-generating compound nitrosoglutathione (GSNO) caused a significant accumulation of 4.4 kb VEGF mRNA, a major VEGF mRNA isoform expressing in chondrocytes. This is the first demonstration that NO can induce VEGF mRNA expression in chondrocytes. VEGF mRNA level was not affected in cells exposed to dibutyryl cGMP, a non-hydrolyzable analog of cGMP, suggesting that the cGMP system is not involved in NO-dependent transcriptional activation of VEGF gene. The GSNO-stimulated induction of VEGF mRNA was slightly attenuated by MAP protein kinase inhibitors PD98058 and SB203580, but was completely blocked in cells incubated with GSNO in the presence of catalase and superoxide dismutase, enzymes scavenging reactive oxygen species (ROS), or in the presence of thiol-containing antioxidants, N-acetyl cysteine and reduced glutathione. These results suggest that in articular chondrocytes the GSNO-induced VEGF gene transcriptional activation is dependent on endogenous ROS production and oxidative thiol modifications.
Turpaev
K
K
Engelhardt Institute of Molecular Biology, ul. Vavilova 32, Russian Academy of Sciences, 117984, Moscow, Russia. turpaev@imb.ac.ru
Litvinov
D
D
Dubovaya
V
V
Panasyuk
A
A
Ivanov
D
D
Prassolov
V
V
D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D048728:MAP Kinase Kinase Kinase 1; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008222:Lymphokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D002374:Catalase; D013482:Superoxide Dismutase; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human