罗格列酮对内皮素-1诱导的大鼠心肌细胞增殖的抑制作用：蛋白激酶C-原癌基因c-fos途径的作用

[Inhibitory effects of rosiglitazone against endothelin-1-induced proliferation of rat cardiac myocytes: the role of PKC-c-fos pathway].

作者信息

Zhu Xiao-Xing, Niu Xiao-Lin, Chen Ding-Zhang, Zhou Xiao-Dong, Pei Jian-Ming, Zhu Miao-Zhang, Guo Jun, Zhu Xiao-Ling, Wang Wen-Qing

机构信息

Department of Cardiology, the Second Affiliated Hosipital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2008 Jun;28(6):1056-60.

PMID:18583263

Abstract

OBJECTIVE

To investigate the mechanism of rosiglitazone (RSG, the activator of peroxisome proliferators activated receptor lambda) for inhibiting endothelin-1 (ET-1)-induced neonatal rat cardiac myocyte hypertrophy and the role of protein kinase C (PKC) and c-fos.

METHODS

In vitro cultured neonatal rat cardiac myocytes were treated with ET-1, phorbol ester (PMA, the PKC activator), ET-1+RSG, ET-1+chelerythrine (che, the PKC inhibitor), PMA+RSG, or without treatment (control), respectively. The effects of RSG on the protein content, (3)H-leucine incorporation, PKC activity and C-fos protein expression were observed in the cardiac myocytes stimulated with ET-1 or PMA.

RESULTS

After two days of culture, the intracellular protein content in ET-1 group and PMA group were increased by 15% (339-/+15 microg/ml) and 13% (329-/+14 microg/ml) as compared with the control cells (290-/+13 microg/ml), respectively (P<0.01). Compared with the ET-1 group, cells treated with ET-1+10(-8) mol/L RSG, ET-1+10(-7) mol/L RSG, and ET-1+che showed decreased intracellular protein content by 10% (303-/+14 microg/ml, P<0.05), 12% (292-/+11 microg/ml, P<0.05), and 13% (291-/+12 microg/ml, P<0.01), respectively. The intracellular protein content in PMA+10(-7) mol/LRSG group was decreased by 10% (P<0.05) in comparison with the PMA group. RSG inhibited protein synthesis enhancement and increased (3)H-leucine incorporation induced by ET-1 and PMA, and antagonized the effects of ET-1 and PMA in promoting PKC activity and c-fos protein expression in the myocytes.

CONCLUSION

The inhibitory effect of RSG on ET-1- or PMA-induced myocyte hypertrophy is associated with PKC-c-fos pathway.

摘要

目的

探讨罗格列酮（RSG，过氧化物酶体增殖物激活受体λ激动剂）抑制内皮素-1（ET-1）诱导的新生大鼠心肌细胞肥大的机制以及蛋白激酶C（PKC）和c-fos的作用。

方法

体外培养的新生大鼠心肌细胞分别用ET-1、佛波酯（PMA，PKC激活剂）、ET-1+RSG、ET-1+白屈菜红碱（che，PKC抑制剂）、PMA+RSG处理或不处理（对照）。观察RSG对ET-1或PMA刺激的心肌细胞中蛋白质含量、³H-亮氨酸掺入、PKC活性和C-fos蛋白表达的影响。

结果

培养两天后，ET-1组和PMA组细胞内蛋白质含量分别比对照细胞（290±13μg/ml）增加了15%（339±15μg/ml）和13%（329±14μg/ml）（P<0.01）。与ET-1组相比，用ET-1+10⁻⁸mol/L RSG、ET-1+10⁻⁷mol/L RSG和ET-1+che处理的细胞内蛋白质含量分别降低了10%（303±14μg/ml，P<0.05）、12%（292±11μg/ml，P<0.05）和13%（291±12μg/ml，P<0.01）。与PMA组相比，PMA+10⁻⁷mol/L RSG组细胞内蛋白质含量降低了10%（P<0.05）。RSG抑制ET-1和PMA诱导的蛋白质合成增强并增加³H-亮氨酸掺入，拮抗ET-1和PMA促进心肌细胞PKC活性和c-fos蛋白表达的作用。