Involvement of protein kinase Cα (PKCα) in the early action of angiotensin II type 2 (AT2) effects on neurite outgrowth in NG108-15 cells:: AT2-receptor inhibits PKCα and p21ras activity

被引:16
|
作者
Beaudry, Helene
Gendron, Louis
Guimond, Marie-Odile
Payet, Marcel D.
Gallo-Payet, Nicole
机构
[1] Univ Sherbrooke, Fac Med, Serv Endocrinol, Sherbrooke, PQ J1H 5N4, Canada
[2] Univ Sherbrooke, Fac Med, Dept Physiol & Biophys, Sherbrooke, PQ J1H 5N4, Canada
关键词
D O I
10.1210/en.2006-0411
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The aim of the present study was to investigate whether protein kinase C (PKC) isoforms may be among the putative candidates implicated in the primary effects of the Ang II type 2 (AT(2)) receptor. Western blot analyses revealed the presence of PKC alpha,epsilon,l, and zeta in NG108-15 cells. After a 3-d treatment with 3 nM Go6976, a specific inhibitor of classical PKC isoforms, cells were characterized by the presence of one elongated process similar to that observed after treatment with Ang II or with CGP42112, a selective AT(2) receptor agonist. Similar findings were observed in cells expressing a dominant-negative mutant of PKC alpha(K368A). Inhibition of PKC alpha in NG108-15 cells also decreased cell number and proliferation. In conditions of acute stimulation, Ang II induced a time-dependent and transient inhibition of PKC alpha activity, as well as a decrease in PKC alpha levels associated with the membrane. Treatment of cells with Go6976 was also found to inhibit p21(ras) (between 1-10 min) but stimulated Rap1 activity (1-5 min) in a time-course similar to that of Ang II. Incubation of NG108-15 cells with Go6976 (3 nM) inhibited basal p42/p44(mapk) phosphorylation, but failed to interfere with its activation by the AT(2) receptor, indicating that inhibition of PKC alpha is not directly involved in the Rap1-MEK-p42/p44(mapk) cascade. Taken together, these results indicate that PKC alpha is a primary target of the AT(2) receptor. Inhibition of PKC alpha leads to a decrease in both p21(ras) activity and cell proliferation, which may facilitate AT(2) receptor signaling through p42/p44(mapk), thereby leading to neurite outgrowth.
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页码:4263 / 4272
页数:10
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