9-羧酸蒽诱导心肌细胞表达c-fos及其胞内影响因素的研究  

STUDY ON c- fos EXPRESSION INDUCED BY ANTHRACENE- 9- CARBOXYLIC ACID IN CULTURED CARDIOMYOCYTESAND INTRACELLULAR FACTORS INVOLVED IN ITSREGULATION

作　　者：吕顺艳[1] 朱妙章[1] 周士胜[1] 于军[1] 

机构地区：[1]第四军医大学生理学教研室,西安710032

出　　处：《中国组织化学与细胞化学杂志》2000年第3期280-285,共6页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金资助课题!(N o. 39770 2 81)

摘　　要：近来发现 Cl-通道抑制剂 9-羧酸蒽 (9- AC)可能是一种新型的磷酸酶抑制剂。本研究观察了蛋白激酶 A(PKA)、蛋白激酶 C (PKC)及非特异性磷酸酶抑制剂对 9- AC诱导的新生大鼠培养心肌细胞 c- fos表达的影响 ,同时利用放免法测定了细胞内 c AMP和 c GMP的变化 ,旨在探讨影响 9- AC诱导 c- fos表达的胞内因素。结果显示 ,9- AC (0 .5 m mol/ L )可显著提高心肌细胞 FOS样免疫阳性细胞数及染色强度。该作用不 PCK抑制剂 Chelerythine(1μm ol/ L)预处理的影响 ,而用 PKA抑制剂 H- 89(10 μmol/ L)预处理心肌细胞 ,可减弱 9- AC的作用 ,但 FOS蛋白的表达量仍显著高于基础水平。与之相比 ,相同条件下异丙肾上腺素 (Iso)对 FOS蛋白表达的诱导作用不受 PKC抑制剂影响 ,但 PKA抑制剂可使之完全抑制。非特异性磷酸酶抑制剂钒酸盐 (VO4,1.5 mm ol/ L )亦可显著增强 FOS的表达 ,9- AC不能使该作用进一步增强。放免测定显示9- AC (0 .5 mm ol/ L )对胞内 c AMP和 c GMP无显著性影响 ,而 Iso (10μm ol/ L )可明显升高 c AMP的浓度。结果表明 ,9-AC可诱导培养的新生大鼠心肌细胞表达 c- fos,其胞内作用途径与 PKA的活性部分相关 ,而与 c AMP、c GMP水平及 PKC无关。Recent studies have shown thatanthrancene- 9- carboxylic acid( 9- AC) ,a Cl-channel blocker,may be a new type phosphatase inhibitor.The expression of c- fos protooncogene in responses to 9- AC in cultured neonatal rat cardiac myocytes was observed,and further studies were carried out to examine the possible roles of protein kinase A( PKA) ,protein kinase C( PKC) and the nonspecific phosphatase inhibitor ( VO4 ) in c- fos expression induced by 9- AC;levels of c AMP and c GMP were measured by radioimmunoassay.The results showed that9- AC( 0 .5mmol/L) caused a significant elevation of the number and intensity of FOS- like immunoreactive cells as compared with control group. The responses were not affected by pretreatment with chelerythine ( Chele,1μmol/L ) ,a PKC inhibitor,but partly inhibited by H- 89( 1 0 μmol/L) ,a specific PKA inhibitor.Underthe same conditions,the FOSexpression induced by isoproterenol( Iso) was not affected by pretreatment with chele,but completely blocked by pretreatment with H- 89. VO4 ,a non- specific protein phosphatase inhibitor which also enhanced FOS expression,9- AC failed to produce additional effect in the presence of VO4 . The levels of c AMP and c GMP in9- AC group were not changed obviously,while Iso significantly increased the level of c AMP. The results reveal that9- AC induce c- fosexpression in cultured neonatalcardiomyocytes.This response to 9- AC is partly related to the activity of PKA,but unaffected by PKC or the levels of c AMP and c GMP.Inhibition of the dephosphorylation of the transcription factors involved in the regulation of c- fos expression by9- AC is a likely mechanism by which this occurs.

关 键 词：9-羧酸蒽 心肌细胞 表达 C-FOS 胞内影响因素 蛋白激酶 蛋白磷酸酶 CAMP CGMP 大鼠 

分 类 号：R963[医药卫生—微生物与生化药学] R972[医药卫生—药理学]