姜黄素抑制人晶状体上皮细胞增生过程中蛋白激酶通路的信号转导变化

胡艳红; 黄秀榕; 祁明信; 陈胜; 冯春燕; 柯发杰

doi:10.3760/cma.j.issn.2095-0160.2015.06.005

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中华实验眼科杂志

• 实验研究 •

ENGLISH ABSTRACT

姜黄素抑制人晶状体上皮细胞增生过程中蛋白激酶通路的信号转导变化

作者及单位信息

出版日期： 2015 -06 -10 ·

DOI： 10.3760/cma.j.issn.2095-0160.2015.06.005

Changes of protein kinase regulatory pathway in inhibition of curcumin on human lens epithelial cells proliferation

Authors Info & Affiliations

Hu Yanhong

Department of Ophthalmology, Second Affiliated People's Hospital of Fujian College of Traditional Chinese Medicine, Fuzhou 350003, China

Huang Xiurong

Qi Mingxin

Chen Sheng

Feng Chunyan

Ke Fajie

Published： 2015 -06 -10 ·

DOI： 10.3760/cma.j.issn.2095-0160.2015.06.005

254

APP内阅读

摘要

背景我们先前的研究证实姜黄素可抑制体外培养的人晶状体上皮细胞（LECs）的增生并影响细胞中环磷酸腺苷（cAMP）和环磷鸟嘌呤核苷（cGMP）的信号转导过程，但实际上体内LECs生物学行为的调控机制非常复杂。

目的探讨姜黄素抑制体外培养的HLE-B3细胞增生过程中蛋白激酶（PK）通路的信号转导变化。

方法HLE-B3经培养和传代后分为空白对照组、重组人碱性成纤维细胞生长因子（rhbFGF）组和rhbFGF+姜黄素组。rhbFGF组在培养液中添加10 ng/ml rhbFGF，rhbFGF+姜黄素组在rhbFGF培养的基础上添加20 mg/L姜黄素作用于细胞24 h，利用流式细胞术检测各组细胞内PKA、PKC、PKG和钙调蛋白（CaM）的表达率。

结果空白对照组、rhbFGF组和rhbFGF+姜黄素组HLE-B3细胞中PKA蛋白的表达率分别为（46.847±1.673）%、（33.250±2.242）%和（71.645±2.432）%，rhbFGF组较空白对照组PKA蛋白的表达率明显下降，而rhbFGF+姜黄素组较rhbFGF组明显升高，差异均有统计学意义（ t＝11.904、28.430，均 P<0.01）。空白对照组、rhbFGF组和rhbFGF+姜黄素组细胞中PKC蛋白的表达率分别为（35.575±1.937）%、（50.652±2.068）%和（27.662±4.481）%，PKG蛋白的表达率分别为（63.838±0.486）%、（86.562±1.325）%和（40.733±2.175）%，CaM蛋白的表达率分别为（67.408±1.391）%、（83.887±3.499）%和（53.785±1.942）%，其中rhbFGF组细胞中PKC、PKG和CaM蛋白的表达率均明显低于空白对照组，差异均有统计学意义（均 P<0.01），而rhbFGF+姜黄素组细胞中PKC、PKG和CaM蛋白的表达率均明显低于rhbFGF组，差异均有统计学意义（均 P<0.01）。

结论姜黄素对HLE-B3细胞增生的抑制作用可能与其上调细胞中PKA的表达和下调PKC、PKG和CaM的表达有关。

关键词：姜黄素;蛋白激酶;信号转导;晶状体上皮细胞

ABSTRACT

BackgroundOur previous study showed that curcumin suppresses the proliferation of human lens epithelial cells (LECs) in vitro and has an influence on the signal transduction of cyclic adenosine monophosphate (cAMP) and cyclic guanosinc monophosphate (cGMP). Actually, the regulation for biological behavior of LECs in vivo is complex.

ObjectiveThis study was to investigate the changes of signal transduction of protein kinase (PK) in inhibition of curcumin on human LECs proliferation.

MethodsHLE-B3 was cultured and then divided into the blank control group, recombinant human basic fibroblast growth factor (rhbFGF) group and rhbFGF+ curcumin group.rhbFGF of 10 ng/ml was added in the medium in the rhbFGF group, and 20 mg/L curcumin was added into rhbFGF-induced cell medium for 24 hours in the rhbFGF+ curcumin group.The expression rates of PKA, PKC, PKG and calmodulin (CaM) in the cells were assayed using flow cytometry.

ResultsThe expression rates of PKA protein were (46.847±1.673)%, (33.250±2.242)% and (71.645±2.432)% in the blank control group, rhbFGF group and the rhbFGF+ curcumin group, respectively, and the expression rate of PKA protein was significantly reduced in the rhbFGF group compared with the blank control group ( t=11.904, P<0.01), but the expression rate of PKA protein in the rhbFGF+ curcumin group was significnatly higher than that in the rhbFGF group ( t=28.430, P<0.01). In the blank control group, rhbFGF group and the rhbFGF+ curcumin group, the expression rates of PKC protein in the cells were (35.575±1.937)%, (50.652±2.068)% and (27.662±4.481)%, those of PKG protein were (63.838±0.486)%, (86.562±1.325)% and (40.733±2.175)%, while those of CaM protein were (67.408±1.391)%, (83.887±3.499)% and (53.785±1.942)%, the expression rates of PKC, PKG and CaM were significantly lower in the rhbFGF group in comparison with the blank control group (all at P<0.01), and those in the rhbFGF+ curcumin group were significantly declined in comparison with the rhbFGF group (all at P<0.01).

ConclusionsSuppression of curcumin on HLE-B3 proliferation probably is associated with the up-regulation of PKA expression and down-regulation of PKC, PKG and CaM expression in the cells.

KEYWORDS： Curcumin;Protein kinase;Signal transduction;Lens epithelial cells

Corresponding author: Huang Xiurong, Email: mocdef.eabsaetengnauhiq

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All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

引用本文

胡艳红,黄秀榕,祁明信,等. 姜黄素抑制人晶状体上皮细胞增生过程中蛋白激酶通路的信号转导变化[J]. 中华实验眼科杂志,2015,33(6)：507-511.

DOI:10.3760/cma.j.issn.2095-0160.2015.06.005

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除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

随着白内障手术技术的提高，人工晶状体材料和设计越来越理想，但后囊膜混浊（posterior capsular opacification，PCO）的发生率仍居高不下，尤其在儿童中的发生率更高，目前除了采用Nd：YAG激光治疗外，尚无其他更好的治疗和预防方法，而Nd：YAG激光治疗潜在的风险不容忽视。PCO发生的主要原因是术后残留的晶状体上皮细胞（lens epithelial cells，LECs）增生并向后囊膜移行。姜黄素是姜科植物姜黄提取物中的主要成分，具有抗炎、抗氧化、降血脂、增强单核－巨噬细胞系统的吞噬功能、调节机体免疫力等作用，研究还表明其能抑制细胞增生、诱导细胞凋亡 ^{[
1
,

2
]}。我们前期研究发现，姜黄素能有效抑制体外培养的LECs的增生，诱导LECs内游离Ca ² ⁺浓度升高，上调LECs内环磷酸腺苷（cyclic adenosine monophosphate，cAMP）水平，下调LECs内环磷鸟嘌呤核苷（cyclic guanosinc monophosphate，cGMP）水平 ^{[
3
,

4
,

5
]}。本研究拟在前期研究的基础上进一步从多条蛋白激酶通路来探讨姜黄素抑制HLE-B3细胞系增生的信号转导机制。

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备注信息

通信作者：黄秀榕，Email： mocdef.eabsaetengnauhiq

基金项目：

福建省科技厅青年人才基金项目 (2008F3050) 查看更多基金信息

福建省卫生厅重点课题项目 (wzzb0605) 查看更多基金信息

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