Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest

Liu,Huijun; Liu,Weiwei; Zhou,Xin; Long,Chongde; Kuang,Xielan; Hu,Jie; Tang,Yan; Liu,Lanying; He,Jia; Huang,Zixin; Fan,Yuting; Jin,Guorong; Zhang,Qingjiong; Shen,Huangxuan

doi:10.3892/mmr.2017.6838

Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest

Authors:
- Huijun Liu
- Weiwei Liu
- Xin Zhou
- Chongde Long
- Xielan Kuang
- Jie Hu
- Yan Tang
- Lanying Liu
- Jia He
- Zixin Huang
- Yuting Fan
- Guorong Jin
- Qingjiong Zhang
- Huangxuan Shen
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Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/mmr.2017.6838
Pages: 2069-2074

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Abstract

Oxidative damage is a key factor for the pathogenesis of age‑related macular degeneration (AMD), therefore, anti-oxidative stress is a valuable method for the prevention or treatment of AMD. The aim of the present study was to reveal the protective mechanism of lutein on retinal pigment epithelium (RPE) cells subjected to oxidative stress. Acute retinal pigment epithelial 19 (ARPE‑19) cells were exposed to oxidative stress induced by H2O2 following lutein pretreatment. The activities of caspases, level of intracellular reactive oxygen species (ROS) and cell cycle were analyzed using flow cytometry. The expression levels of cell cycle regulatory proteins and inflammation‑associated genes were detected using western blot and reverse transcription‑polymerase chain reaction analyses, respectively. The data showed that oxidative stress reduced cell viability, and increased total apoptosis and ROS generation, however, lutein prevented cells from oxidative stress‑induced damage. In addition, oxidative damage triggered G2/M phase arrest of the ARPE‑19 cells, which was reversed by lutein in a concentration‑dependent manner, through the activation of cyclin‑dependent kinase 1 and cell division cycle 25C, and degradation of cyclin B1. These results demonstrated that lutein may be an effective antioxidant, which can be applied in the prevention of AMD, or other age-related diseases associated with oxidative damage.

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1	Koushan K, Rusovici R, Li W, Ferguson LR and Chalam KV: The role of lutein in eye-related disease. Nutrients. 5:1823–1839. 2013. View Article : Google Scholar : PubMed/NCBI
2	Holz FG, Schmitz-Valckenberg S and Fleckenstein M: Recent developments in the treatment of age-related macular degeneration. J Clin Invest. 124:1430–1438. 2014. View Article : Google Scholar : PubMed/NCBI
3	Wenzel A, Grimm C, Samardzija M and Remé CE: Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res. 24:275–306. 2005. View Article : Google Scholar : PubMed/NCBI
4	Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M and Nyland J: Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: The Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 75:216–230. 2004. View Article : Google Scholar : PubMed/NCBI
5	Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, et al: Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 272:1413–1420. 1994. View Article : Google Scholar : PubMed/NCBI
6	Zarbin MA: Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 122:598–614. 2004. View Article : Google Scholar : PubMed/NCBI
7	Cai J, Nelson KC, Wu M, Sternberg P Jr and Jones DP: Oxidative damage and protection of the RPE. Prog Retin Eye Res. 19:205–221. 2000. View Article : Google Scholar : PubMed/NCBI
8	Liang FQ and Godley BF: Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: A possible mechanism for RPE aging and age-related macular degeneration. Exp Eye Res. 76:397–403. 2003. View Article : Google Scholar : PubMed/NCBI
9	Kang KH, Lemke G and Kim JW: The PI3K-PTEN tug-of-war, oxidative stress and retinal degeneration. Trends Mol Med. 15:191–198. 2009. View Article : Google Scholar : PubMed/NCBI
10	Tan JS, Wang JJ, Flood V, Rochtchina E, Smith W and Mitchell P: Dietary antioxidants and the long-term incidence of age-related macular degeneration: The Blue Mountains Eye Study. Ophthalmology. 115:334–341. 2008. View Article : Google Scholar : PubMed/NCBI
11	Bian Q, Gao S, Zhou J, Qin J, Taylor A, Johnson EJ, Tang G, Sparrow JR, Gierhart D and Shang F: Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells. Free Radic Biol Med. 53:1298–1307. 2012. View Article : Google Scholar : PubMed/NCBI
12	Silvan JM, Reguero M and de Pascual-Teresa S: A protective effect of anthocyanins and xanthophylls on UVB-induced damage in retinal pigment epithelial cells. Food Funct. 7:1067–1076. 2016. View Article : Google Scholar : PubMed/NCBI
13	Sommerburg O, Keunen JE, Bird AC and van Kuijk FJ: Fruits and vegetables that are sources for lutein and zeaxanthin: The macular pigment in human eyes. Br J Ophthalmol. 82:907–910. 1998. View Article : Google Scholar : PubMed/NCBI
14	Obana A, Hiramitsu T, Gohto Y, Ohira A, Mizuno S, Hirano T, Bernstein PS, Fujii H, Iseki K, Tanito M and Hotta Y: Macular carotenoid levels of normal subjects and age-related maculopathy patients in a Japanese population. Ophthalmology. 115:147–157. 2008. View Article : Google Scholar : PubMed/NCBI
15	Age-Related Eye Disease Study 2 Research Group, . Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The age-related eye disease study 2 (AREDS2) randomized clinical trial. JAMA. 309:2005–2015. 2013. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Abdel-AAl el SM, Akhtar H, Zaheer K and Ali R: Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients. 5:1169–1185. 2013. View Article : Google Scholar : PubMed/NCBI
18	Aimjongjun S, Sutheerawattananonda M and Limpeanchob N: Silk lutein extract and its combination with vitamin E reduce UVB-mediated oxidative damage to retinal pigment epithelial cells. J Photochem Photobiol B. 124:34–41. 2013. View Article : Google Scholar : PubMed/NCBI
19	Stark GR and Taylor WR: Control of the G2/M transition. Mol Biotechnol. 32:227–248. 2006. View Article : Google Scholar : PubMed/NCBI
20	Yang JI, Yeh CC, Lee JC, Yi SC, Huang HW, Tseng CN and Chang HW: Aqueous extracts of the edible Gracilaria tenuistipitata are protective against H2O2-induced DNA damage, growth inhibition and cell cycle arrest. Molecules. 17:7241–7254. 2012. View Article : Google Scholar : PubMed/NCBI
21	Li L, Gu B, Zhou F, Chi J, Wang F, Peng G, Xie F, Qing J, Feng D, Lu S and Yao K: Human herpesvirus 6 suppresses T cell proliferation through induction of cell cycle arrest in infected cells in the G2/M phase. J Virol. 85:6774–6783. 2011. View Article : Google Scholar : PubMed/NCBI
22	Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, Curletti CR, Hancox LS, Hu J, Ebright JN, Malek G, et al: The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited. Prog Retin Eye Res. 29:95–112. 2010. View Article : Google Scholar : PubMed/NCBI
23	Cherepanoff S, McMenamin P, Gillies MC, Kettle E and Sarks SH: Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration. Br J Ophthalmol. 94:918–925. 2010. View Article : Google Scholar : PubMed/NCBI
24	Li SY, Fung FK, Fu ZJ, Wong D, Chan HH and Lo AC: Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: In vivo and in vitro studies. Invest Ophthalmol Vis Sci. 53:5976–5984. 2012. View Article : Google Scholar : PubMed/NCBI
25	Murthy RK, Ravi K, Balaiya S, Brar VS and Chalam KV: Lutein protects retinal pigment epithelium from cytotoxic oxidative stress. Cutan Ocul Toxicol. 33:132–137. 2014. View Article : Google Scholar : PubMed/NCBI