Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells
	Wei, Yan 1; Wang, Xu 2; Wang, Ling 1
刊名	MOLECULAR VISION
	2009-06-14
卷号	15 期号:132-33 页码:1243-1251
ISSN号	1090-0535
文献子类	Article
英文摘要	Purpose: Cannabinoid receptors have been detected in neuron cells and proposed as potential therapeutic agents in neurodegenerative disorders because of their involvement in controlling neural cell survival and death. However, their presence and role in human retinal pigment epithelial (RPE) cells, which play a key role in initiating and developing age related macular degeneration (ARMD), have never been investigated. Here we analyzed the expression of and changes in cannabinoid receptors (CB1 and CB2) and one enzyme responsible for endocannabinoid hydrolysis, fatty acid amide hydrolase (FAAH), in RPE cell oxidative damage process, a cellular model of ARMD. Methods: Primary human RPE cells and cells from the ARPE-19 cell line were cultured and exposed to H2O2 for 24 h to induce oxidative damage. Real time RT-PCR, immunofluorescent staining, and western blot methods were performed to study the expression of and changes in CB1 and CB2 receptors, and FAAH. Cell viability and reactive oxygen species (ROS) production were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and a dichlorofluorescein (DCF) assay, respectively. PI3K/Akt and ERK1/2 protein expression and activation of signaling molecules were assessed by western blot analysis. Results: By using real time RT-PCR, immunofluorescent staining and western blot methods, we showed that human RPE cells express CB1, CB2, and FAAH. Meanwhile, oxidative stress can upregulate CB1 and CB2 receptor expression, and downregulate FAAH expression. The CB1/CB2 receptor agonist, CP55,940, and the CB2 receptor agonist, JWH015 significantly protected RPE cells from oxidative damage. In addition, CP55,940 significantly reduced the levels of intracellular ROS, strengthened oxidative stress-induced activation of PI3K/Akt and reduced activation of the ERK1/2 signal pathway. Conclusions: The results demonstrate the expression and regulation of CB1 and CB2 receptors and FAAH in human RPE cells. The modulation of cannabinoid receptor tone warrants consideration for future therapeutic strategies of ARMD.
资助项目	Shanghai Leading Academic Discipline[S30205] ; Shanghai Science and Technology Committee[08JC1415600]
WOS关键词	MITOCHONDRIAL-DNA DAMAGE ; MACULAR DEGENERATION ; ENDOCANNABINOID SYSTEM ; MULTIPLE-SCLEROSIS ; ENDOGENOUS CANNABINOIDS ; INDUCED NEUROTOXICITY ; PARKINSONS-DISEASE ; OXIDATIVE STRESS ; GOLDFISH RETINA ; BIPOLAR CELLS
WOS研究方向	Biochemistry & Molecular Biology ; Ophthalmology
语种	英语
出版者	MOLECULAR VISION
WOS记录号	WOS:000267986500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279211]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Wang, Ling
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Ophthalmol, Shanghai 200025, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Wei, Yan,Wang, Xu,Wang, Ling. Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells[J]. MOLECULAR VISION,2009,15(132-33):1243-1251.
APA	Wei, Yan,Wang, Xu,&Wang, Ling.(2009).Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells.MOLECULAR VISION,15(132-33),1243-1251.
MLA	Wei, Yan,et al."Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells".MOLECULAR VISION 15.132-33(2009):1243-1251.