Reactive Oxygen Species Are Critical in the Oleic Acid-Mediated Mitogenic Signaling Pathway in Vascular Smooth Muscle Cells
作者:
Gang Lu,
Eddie L. Greene,
Toshi Nagai,
Brent M. Egan,
期刊:
Hypertension
(OVID Available online 1998)
卷期:
Volume 32,
issue 6
页码: 1003-1010
ISSN:0194-911X
年代: 1998
出版商: OVID
数据来源: OVID
摘要:
8-fold of that seen in control cells at 5 minutes. This was blocked by catalase, which suggests that H2O2was the principal ROS. The oleic acid-induced increases in H2O2were blocked when PKC was inhibited with the use of bisindolylmaleimide and when PKC activity was downregulated by exposing RASMCs to phorbol 12-myristate 13-acetate for 24 hours. Stearic and elaidic acids, which are weak PKC activators, did not significantly increase H2O2production. The increase of H2O2in response to oleic acid was inhibited by the antioxidant N-acetylcysteine. N-Acetylcysteine also completely blocked ERK activation and the increase of thymidine incorporation in response to oleic acid. The data suggest that generation of H2O2in RASMCs exposed to oleic acid is PKC dependent. Moreover, H2O2production emerges as a critical intermediary event in the oleic acid-mediated mitogenic signaling pathway between the activation of PKC and ERK. These observations raise the possibility that the elevated plasma nonesterified fatty acids, including oleic acid, in obese hypertensive patients contribute to vascular growth and remodeling by a PKC-dependent mechanism to generate ROS that subsequently activate ERK. (Hypertension. 1998;32:1003-1010.)
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