FEBS Letters | |
Troglitazone inhibits angiotensin II‐induced extracellular signal‐regulated kinase 1/2 nuclear translocation and activation in vascular smooth muscle cells | |
Xi, Xiao-Ping1  Goetze, Stephan1  Law, Ronald E.1  Graf, Kristof2  Hsueh, Willa A.1  Fleck, Eckart2  | |
[1] University of California, Los Angeles, School of Medicine, Division of Endocrinology, Diabetes and Hypertension, Warren Hall, Second Floor, Suite 24-130, 900 Veteran Avenue, Box 957073, Los Angeles, CA 90095, USA;Department of Medicine/Cardiology, Virchow Klinikum, Humboldt University Berlin and German Heart Institute Berlin, 13353 Berlin, Germany | |
关键词: Extracellular signal-regulated kinase 1/2; Protein kinase Cζ; Vascular smooth muscle cell; Troglitazone; Angiotensin II; TRO; troglitazone; VSMC; vascular smooth muscle cell; AII; angiotensin II; ERK; extracellular signal-regulated kinase; MAPK; mitogen-activated protein kinase; MEK; MAPK ERK kinase; PKCζ; protein kinase Cζ; PPARγ; peroxisome proliferator-activated receptor γ; MBP; myelin basic protein; | |
DOI : 10.1016/S0014-5793(99)00624-9 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
The thiazolidinedione troglitazone inhibits angiotensin II-induced extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activity in vascular smooth muscle cells. Activation of extracellular signal-regulated kinase 1/2 by angiotensin II is a multistep process involving both its phosphorylation by mitogen-activated protein kinase extracellular signal-regulated kinase kinase in the cytoplasm and a subsequent translocation to the nucleus. The cytoplasmic activation of extracellular signal-regulated kinase 1/2 in vascular smooth muscle cells proceeds through the protein kinase Cζ→mitogen-activated protein kinase extracellular signal-regulated kinase kinase→extracellular signal-regulated kinase pathway. Troglitazone did not affect the angiotensin II-induced activation of protein kinase Cζ or its downstream signaling kinases extracellular signal-regulated kinase 1/2 in the cytosol. In contrast, angiotensin II-induced activation of protein kinase Cζ and extracellular signal-regulated kinase 1/2 in the nucleus were both inhibited by troglitazone. Nuclear translocation of extracellular signal-regulated kinase 1/2 induced by angiotensin II was completely blocked by troglitazone. Protein kinase Cζ, however, did not translocate upon angiotensin II stimulation. Troglitazone, therefore, inhibits both angiotensin II-induced nuclear translocation of extracellular signal-regulated kinase 1/2 and the nuclear activity of its upstream signaling kinase protein kinase Cζ. Since extracellular signal-regulated kinase 1/2 nuclear translocation may be a critical signaling step for multiple growth factors that stimulate vascular smooth muscle cells proliferation and migration, troglitazone may provide a new therapeutical approach for the prevention and treatment of atherosclerosis and restenosis.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201912020307808ZK.pdf | 296KB | download |