PURPOSE Oxidative stress and mitochondrial oxidative damage have been implicated in aging and many common diseases. Mitochondria are a primary source of reactive oxygen species (ROS) in the cell, and are particularly susceptible to oxidative damage. In the present work, we examined the ability of a novel cell-penetrating, mitochondria-targeted peptide antioxidant in protecting against oxidant-induced mitochondrial dysfunction and apoptosis in Rat Retinal Photoreceptors.
METHODS Rat retina neurons in 3-day cultures, with or without MTP-131, were treated with the oxidant tert-butyl hydroperoxide (t-BHP). Apoptosis, photoreceptor differentiation and protein peroxidation were evaluated. A quantitative analysis of apoptotic photoreceptor cells was performed in four independent experiments by staining nucleus with hoechst, and a significant increase in pyknotic or fragmented nuclei was observed in 661w cells after t-BHP treatment for 0.5 h (43.1 ± 11.7%) compared with untreated control cultures (14.7 ± 5.5%, p ＜ 0.01). Application of 100nM MTP-131 significantly reduced abnormal nuclei cells to 19.5 ± 6.8% (p＜ 0.01) compared with t-BHP treated group.
RESULTS Addition of SS-31 reduced photoreceptor apoptosis by almost half, simultaneously preserving their mitochondrial membrane integrity. MTP-131 also enhanced photoreceptor differentiation, and reduced tBHP-induced protein peroxidation.
CONCLUSIONS These results show for the first time the protective role of SS-31 in oxidative stress-induced apoptosis in retinal neurons . SS-31 represents a novel platform of mitochondria-targeted antioxidants with broad therapeutic potential. |
