Involvement of reactive oxygen species in the activation of tyrosine kinase and extracellular signal-regulated kinase by angiotensin II.
Reactive oxygen species (ROS) have been proposed to mediate vascular hypertrophy induced by angiotensin II (Ang II). Recently, we and others have shown that growth-promoting signals by Ang II involve protein tyrosine kinase (PTK) and extracellular signal-regulated kinase (ERK). However, whether ROS contribute to the Ang II-induced PTK and/or ERK activation in vascular smooth muscle cells (VSMCs) remains largely unclear. Here, we have investigated the possible involvement of ROS in Ang II-induced PTK and ERK activation. In the presence of a NADH/NADPH oxidase inhibitor, diphenyleneiodonium (DPI) or an antioxidant, alpha-tocopherol, Ang II-induced protein tyrosine phosphorylation of two major proteins (p120, p70) and ERK activation were markedly reduced, whereas ERK activation by epidermal growth factor was unaffected. DPI also inhibited Ang II-induced H2O2 production and PTK activation. In this regard, H2O2 and a membrane permeable thiol-oxidizing agent, diamide, stimulated protein tyrosine phosphorylation of p120 and p70, and ERK activation in VSMCs. H2O2 also enhanced PTK activity. From these data, we conclude that ROS play a critical role in the Ang II-induced PTK and ERK activation in VSMCs, thereby contributing to vascular growth associated with enhanced Ang II activity.
Frank
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GD
Department of Anatomy and Physiology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Eguchi
S
S
Yamakawa
T
T
Tanaka
S
S
Inagami
T
T
Motley
E D
ED
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020536:Enzyme Activators / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007202:Indicators and Reagents; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D020536:Enzyme Activators; D007202:Indicators and Reagents; D016877:Oxidants; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases