Troglitazone inhibits angiotensin II‐induced extracellular signal‐regulated kinase 1/2 nuclear translocation and activation in vascular smooth muscle cells

FEBS Letters

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