title: The role of melatonin as an antioxidant in human lens epithelial cells.
abstract: Oxidative stress plays a significant role in pathophysiology of cataracts and also known to affect the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway. This well-documented pathway is involved in protecting against apoptosis-inducing insults, including oxidative stress. Melatonin (N-acetyl-5-methoxy-tryptamine), the major secretory product of the pineal gland, was identified as a powerful free radical scavenger and a broad-spectrum antioxidant that defends against various oxidative stress-associated diseases. This study was conducted to determine whether melatonin could prevent hydrogen peroxide (H₂O₂)-induced oxidative stress in human lens epithelial cells (HLECs) and to elucidate the molecular pathways involved in this protection. HLECs were subjected to various concentrations of H₂O₂ in the presence or absence of melatonin at different concentrations. Cell viability was monitored by a 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl-tetrazoliumbromide (MTT) assay, and the apoptosis rate and intracellular reactive oxygen species (ROS) levels were measured by flow cytometry using annexin V-FITC and propidium iodide (PI) staining. The expression levels of HO-1, Nrf-2, CAT, and MDA were measured using Western blot analysis. Akt activation was also evaluated by Western blot analysis. The data from our study showed that cells pretreated with melatonin can reduce H₂O₂-induced intracellular ROS generation and thus protect HLECs from cell apoptosis. Furthermore, we found that melatonin is a potent activator of Akt in HLECs. Our findings suggest that in addition to functioning as a direct free radical scavenger, melatonin can elicit cellular signaling pathways that are protective against oxidative stress-induced cataracts.
authors.affiliation: Key Laboratory of Harbin Medical University Eye Center, Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Bai
authors.forename: L
authors.initials: L
authors.lastname: Dong
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: H
authors.initials: H
authors.lastname: Ge
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Liu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007908:Lens, Crystalline / Q000166:cytology*; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D008550:Melatonin