title: Protective effect of mitochondria‑targeted peptide MTP‑131 against oxidative stress‑induced apoptosis in RGC‑5 cells.
abstract: The retina of the human eye is extremely vulnerable to oxidative damage. Previous studies have demonstrated that oxidative stress is the predominant mechanism associated with the pathogenesis of age‑related macular degeneration, diabetic retinopathy, glaucoma and retinitis pigmentosa. MTP‑131, a novel mitochondria‑targeted peptide, has been demonstrated to specifically concentrate in the inner mitochondria membrane and to exhibit remarkable antioxidant effects both in vitro and in animal models. In the present study, the protective effect of MTP‑131 was evaluated in response to hydrogen peroxide (H2O2)‑induced oxidative damage in a retinal ganglion cell line, RGC‑5. Cell viability was measured by lactate dehydrogenase (LDH) assay. Changes of mitochondrial membrane potential and generation of intracellular reactive oxygen species (ROS) were measured by flow cytometry and confocal microscopy, respectively. Annexin V‑fluorescein isothiocyanate/propidium iodide staining was used for assessment of apoptosis. Release of cytochrome c was analyzed by confocal microscopy. Pretreatment of cells with MTP‑131 inhibited H2O2‑induced cytotoxicity and reduced LDH release in a dose‑dependent manner, compared with cells treated with H2O2 alone. Mitochondrial depolarization and ROS generation were also prevented by MTP‑131 pretreatment. In addition, MTP‑131 pretreatment inhibited cytochrome c release from mitochondria to cytoplasm, and significantly reduced apoptosis in RGC‑5 cells, compared with cells treated with H2O2 alone. In conclusion, mitochondria‑targeted peptide MTP‑131 exhibited a protective effect against oxidative stress‑induced apoptosis in RGC‑5 cells, which may provide a novel approach for the treatment of age‑associated retinal diseases.
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Kaijun
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D009842:Oligopeptides; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D045304:Cytochromes c; D006861:Hydrogen Peroxide