Administration of dexamethasone up-regulates protein kinase C activity and the expression of γ and ε protein kinase C isozymes in the rat brain

被引:32
作者
Dwivedi, Y [1 ]
Pandey, GN [1 ]
机构
[1] Univ Illinois, Dept Psychiat, Inst Psychiat, Chicago, IL 60612 USA
关键词
cortex; dexamethasone; glucocorticoids; hippocampus; hypothalamic-pituitary-adrenal axis; rat brain; protein kinase C;
D O I
10.1046/j.1471-4159.1999.0720380.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Altered hypothalamic-pituitary-adrenal (HPA) function (increased plasma coitisol level) has been shown to be associated with mood and behavior. Protein kinase C (PKC), an important component of the phosphatidylinositol signal transduction system, plays a major role in mediating various physiological functions. The present study investigates the effects of acute (single) and repeated (10-day) administrations of 0.5 or 1.0 mg/kg doses of dexamethasone (DEX), a synthetic glucocorticoid, on B-max and K-D of [H-3]phorbol 12,13-dibutyrate ([H-3]PDBu) binding, PKC activity, and protein expression of PKC isozymes alpha, beta, gamma, delta, and epsilon in the membrane and the cytosolic fractions of rat cortex and hippocampus. It was observed that repeated administration of 1.0 mg/kg DEX for 10 days caused a significant increase in B-max of [H-3]PDBu binding to PKC, in PKC activity, and in expressed protein levels of the gamma and epsilon isozymes in both the cytosolic and the membrane fractions of the cortex and the hippocampus, whereas a lower dose of DEX (0.5 mg/kg for 10 days) caused these changes only in the hippocampus. On the other hand, a single administration of DEX (0.5 or 1.0 mg/kg) had no significant effect on PKC in the cortex or in the hippocampus. These results suggest that alterations in HPA function from repeated administration of glucocorticoids may modulate PKC-mediated functions.
引用
收藏
页码:380 / 387
页数:8
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