Möritz K U, Walter R, Leopold K, Hadasová E, Engel G, Siegmund W
Institut für Pharmakologie, Ernst-Moritz-Arndt-Universität Greifswald, Germany.
Pharmazie. 1998 Apr;53(4):268-71.
Immunostimulants known to initiate cytokine production were found to decrease the activity of hepatic microsomal drug oxidative enzymes but to activate protein kinase C (PKC). The present study investigated the effects of immunostimulating doses of rat interferon-gamma (IFN, 670,000 units i.p.) and streptolysin O (SLO, 100 HU/kg i.v. for 5 days) on hepatic soluble, membrane-bound and nuclear PKC, 7-ethylresorufin-O-deethylase (EROD) and 7-pentylresorufin-O-deethylase (PROD) in male Wistar rats. The SLO- and IFN-mediated decrease of EROD and PROD activity was associated with a characteristic activation of the hepatic and spleenic PKC. In SLO- and IFN-treated animals activities of the cytosolic, membrane-bound and nuclear PKC were significantly higher than in respective controls. Our results suggest that a decrease in hepatic cytochrome P450 content as well as the decrease in the EROD and PROD activities are inversely related to the function of PKC.
已知能引发细胞因子产生的免疫刺激剂可降低肝微粒体药物氧化酶的活性,但能激活蛋白激酶C(PKC)。本研究调查了免疫刺激剂量的大鼠γ干扰素(IFN,腹腔注射670,000单位)和链球菌溶血素O(SLO,静脉注射100 HU/kg,持续5天)对雄性Wistar大鼠肝脏可溶性、膜结合型和核型PKC、7-乙基试卤灵-O-脱乙基酶(EROD)和7-戊基试卤灵-O-脱乙基酶(PROD)的影响。SLO和IFN介导的EROD和PROD活性降低与肝脏和脾脏PKC的特征性激活有关。在SLO和IFN处理的动物中,胞质、膜结合型和核型PKC的活性显著高于各自的对照组。我们的结果表明,肝脏细胞色素P450含量的降低以及EROD和PROD活性的降低与PKC的功能呈负相关。