Details

Autor(en) / Beteiligte

• Kito, Hiroyuki
• Chen, Emery L
• Wang, Xiujie
• Ikeda, Masataka
• Azuma, Nobuyoshi
• Nakajima, Nobuyuki
• Gahtan, Vivian
• Sumpio, Bauer E

Titel

Role of mitogen-activated protein kinases in pulmonary endothelial cells exposed to cyclic strain

Ist Teil von

• Journal of applied physiology (1985), 2000-12, Vol.89 (6), p.2391-2400

Ort / Verlag

Bethesda, MD: Am Physiological Soc

Erscheinungsjahr

2000

Quelle

MEDLINE

Beschreibungen/Notizen

• 1  First Department of Surgery, Chiba University School of Medicine, Chiba 260, Japan; and 2  Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510 The aim of this study was to examine the role of mitogen-activated protein kinases (MAPKs) activation in bovine pulmonary arterial endothelial cells (EC) exposed to cyclic strain. EC were subjected to 10% average strain at 60 cycles/min. Cyclic strain induced activation of extracellular signal-regulated kinase (ERK; 1.5-fold), c-Jun NH 2 -terminal protein kinase (JNK; 1.9-fold), and p38 (1.5-fold) with a peak at 30 min. To investigate the functional role of the activated MAPKs, we analyzed cells after treatment with PD-98059, a specific ERK kinase inhibitor, or SB-203580, a catalytic inhibitor for p38, and after transient transfection with JNK(K-R), and MEKK(K-M) the respective catalytically inactive mutants of JNK1 and MAPK kinase kinase-1. Cyclic strain increased activator protein-1 (AP-1) binding activity, which was blocked by PD-98059 and SB-203580. Activity of AP-1-dependent luciferase reporter driven by 12- O -tetradecanoyl-phorbol-13-acetate-responsive element (TRE) was induced by cyclic strain, and this was attenuated by PD-98059, MEKK(K-M), JNK(K-R), and SB-203580. PD-98059 and SB-203850 did not inhibit cell alignment and migration induced by cyclic strain. MEKK(K-M) and JNK(K-R) transfection did not block cyclic strain-induced cell alignment. In conclusion, cyclic strain activates ERK, JNK, and p38, and their activation plays a role in transcriptional activation of AP-1/TRE but not in cell alignment and migration changes in bovine pulmonary arterial EC. activator protein-1; mechanical stress