N-acetylcysteine inhibits angiotensin ii-mediated activation of extracellular signal-regulated kinase and epidermal growth factor receptor.
Angiotensin II (Ang II) is known to stimulate reactive oxygen species (ROS) generation and epidermal growth factor (EGF) receptor transactivation to mediate growth-promoting signals such as extracellular signal-regulated kinase (ERK) in vascular smooth muscle cells (VSMCs). However, how ROS and EGF receptor interact to orchestrate these signals in VSMCs remains unclear. Here we found that an antioxidant, N-acetylcysteine, inhibited ERK activation and EGF receptor tyrosine phosphorylation induced by Ang II. Moreover, H(2)O(2) stimulates EGF receptor tyrosine phosphorylation and EGF receptor inhibitors attenuated H(2)O(2)-induced ERK activation. These data indicate that ROS mediate Ang II-induced EGF receptor transactivation, a critical mechanism for ERK-dependent growth in VSMCs.
Frank
G D
GD
Department of Anatomy and Physiology, Meharry Medical College, Nashville, Tennessee, 37208, USA.
Eguchi
S
S
Inagami
T
T
Motley
E D
ED
D000111:Acetylcysteine / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013997:Time Factors; D015533:Transcriptional Activation; D020032:Tyrphostins / Q000494:pharmacology
C107875:6-(methylamino)pyrido(3,4-d)pyrimidine; D000975:Antioxidants; D007476:Ionophores; D011743:Pyrimidines; D011799:Quinazolines; D017382:Reactive Oxygen Species; D020032:Tyrphostins; D000804:Angiotensin II; C101044:RTKI cpd; D000001:Calcimycin; D006861:Hydrogen Peroxide; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D000111:Acetylcysteine