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(R,R)-XY-10和(S,S)-XY-10诱导视网膜色素上皮细胞增殖及其作用机制。

Proliferation of retinal pigment epithelial cells induced by (R,R)-XY-10 and (S,S)-XY-10 and their action mechanisms.

作者信息

Cheng Yu-Wen, Wang Yu-Liang, Zhang Yi-Hua, Peng Si-Xun, Chiou George C Y

机构信息

Institute of Ocular Pharmacology, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843, USA.

出版信息

Int J Ophthalmol. 2010;3(1):9-13. doi: 10.3980/j.issn.2222-3959.2010.01.03. Epub 2010 Mar 18.

Abstract

AIM

To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells (ARPE-19).

METHODS

Human retinal pigmented epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth, and their mechanisms of proliferative action by using ERK, AKT, PI3K, Protein kinase C (PKC) and Nitric oxide synthase (NOS) inhibitors.

RESULTS

(R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation, but not on HUVECs. When treated with proliferative inhibitors, H-7 (5µmol/L), hypericin (20µmol/L), PD98059 (2µmol/L), LY294002 (50µmol/L), SH-5 (10µmol/L) and L-NAME (100µmol/L), the proliferative effect was reduced by H-7, hypericin, PD98059 and LY294002, but not by SH-5 and L-NAME.

CONCLUSION

(R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway.

摘要

目的

研究(R,R)-XY-10和(S,S)-XY-10对视网膜色素上皮细胞(ARPE-19)增殖作用的机制。

方法

采用人视网膜色素上皮细胞(ARPE-19)和人脐静脉内皮细胞(HUVECs),研究(R,R)-XY-10和(S,S)-XY-10对细胞生长的影响,以及使用ERK、AKT、PI3K、蛋白激酶C(PKC)和一氧化氮合酶(NOS)抑制剂探讨其增殖作用机制。

结果

(R,R)-XY-10和(S,S)-XY-10能剂量依赖性地增加ARPE-19细胞增殖,但对HUVECs无此作用。当用增殖抑制剂H-7(5μmol/L)、金丝桃素(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5(10μmol/L)和L-NAME(100μmol/L)处理时,H-7、金丝桃素、PD98059和LY294002可降低增殖作用,但SH-5和L-NAME无此作用。

结论

(R,R)-XY-10和(S,S)-XY-10可通过MAPK和PI3K依赖性途径诱导细胞增殖。

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