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Abstract #46422 Published in IGR 13-3
Mitochondria-Targeted Peptide MTP-131 Alleviates Mitochondrial Dysfunction and Oxidative Damage in Human Trabecular Meshwork Cells
Chen M; Liu B; Gao Q; Zhuo Y; Ge JInvestigative Ophthalmology and Visual Science 2011; 52: 7027-7037
PURPOSE: To investigate the antioxidative ability of a novel mitochondria-targeted peptide MTP-131 in immortalized human trabecular meshwork (iHTM) and glaucomatous human trabecular meshwork (GTM(3)) cell lines. METHODS: Cultured iHTM and GTM(3) cells were pretreated with MTP-131 for 1 hour, and sustained oxidative stress was induced by subjecting TM cells to 200 μM hydrogen peroxide (H(2)O(2)) for 24 hours. Untreated cells and cells incubated with H(2)O(2) alone were used as controls. Lactate dehydrogenase (LDH) assay was used to determine cell viability. Changes of mitochondrial membrane potential (ΔΨm) and generation of intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and confocal microscopy. Activation of caspase 3 was quantified by Western blotting, and apoptosis was measured by flow cytometry. Release of cytochrome c and changes in cytoskeleton were analyzed by confocal microscopy. Data were analyzed with commercial data analysis software and P < 0.05 was considered to be statistically significant. RESULTS: In both iHTM and GTM(3) cells, decrease of ΔΨm and elevation of intracellular ROS were detected after sustained oxidative stress induced by H(2)O(2). When cells were pretreated with MTP-131, the H(2)O(2)-induced mitochondrial depolarization was prevented; intracellular ROS, LDH release, and apoptosis were significantly decreased; release of cytochrome c from mitochondria to cytoplasm and activation of caspase 3 were inhibited. In addition, cytoskeleton changes caused by H(2)O(2) were also alleviated by MTP-131. CONCLUSIONS: Mitochondria-targeted peptide MTP-131 could prevent both iHTM and GTM(3) cells from sustained oxidative stress induced by H(2)O(2).
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P.R. China.
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
1.3 Pathogenesis (Part of: 1 General aspects)
3.8 Pharmacology (Part of: 3 Laboratory methods)
