ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells

被引:50
作者
Freeman, EJ
Ruehr, ML
Dorman, RV
机构
[1] Akron Gen Med Ctr, Dept Internal Med, Calhoun Res Lab, Akron, OH 44307 USA
[2] Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1998年 / 274卷 / 01期
关键词
angiotensin II; arachidonic acid; cytosolic phospholipase A(2); angiotensin receptors;
D O I
10.1152/ajpcell.1998.274.1.C282
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The accumulation of radiolabeled arachidonic acid (AA), immunoblot analysis of subcellular fractions, and immunofluorescence tagging of proteins in intact cells were used to examine the coupling of ANG II receptors with the activity and location of a cytosolic phospholipase A(2) (cPLA(2)) in vascular smooth muscle cells (VSMC). ANG II induced the accumulation of AA, which peaked by 10 min and was downregulated by 20 min. A large proportion of the AA released in response to ANG II was due to the activation of a Ca2+-dependent lipase coupled to an AT(1) receptor. However, regulation of Ca2+ availability failed to completely block AA release, and a small but significant reduction in ANG II-mediated AA release was observed in the presence of an AT(2) antagonist. These findings, coupled with a 25% reduction in the ANC II-induced AA release by an inhibitor specific for a Ca2+-independent PLA(2), are consistent with the presence and activation of a Ca2+-independent PLA(2). In contrast, immunoblot analysis and immunofluorescence detection showed that the ANG II-mediated translocation of cPLA(2) to a membrane fraction was exclusively AT(1) dependent and regulated by Ca2+ availability. Furthermore, the nucleus was the membrane target. We conclude that ANG II regulates the Ca2+-dependent activation and translocation of cPLA(2) through an AT(1) receptor and that this event is targeted at the nucleus in VSMC.
引用
收藏
页码:C282 / C288
页数:7
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