A role for DJ-1 against oxidative stress in the mammalian retina

摘要

We have previously reported the expression of Parkinson disease-associated genes encoding alpha-synuclein, parkin and UCH-L1 in the retina across mammals. DJ-1, or parkinsonism-associated deglycase, is a redox-sensitive protein with putative roles in cellular protection against oxidative stress, among a variety of functions, acting through distinct pathways and mechanisms in a wide variety of tissues. Its function in counteracting oxidative stress in the retina, as it occurs in Parkinson and other human neurodegenerative diseases, is, however, poorly understood. In the present study, we address the expression of DJ-1 in the mammalian retina and its putative neuroprotective role in this tissue in a well-known model of parkinsonism, the rotenone-treated rat. As a result, we demonstrate that the DJ1 gene is expressed at both mRNA and protein levels in the neural retina and retinal pigment epithelium (RPE) of all mammalian species studied. We also present evidence that DJ-1 functions in the retina as a sensor of cellular redox homeostasis, which reacts to oxidative stress by increasing its intracellular levels and additionally becoming oxidized. Levels of alpha-synuclein also became upregulated, although parkin and UCH-L1 expression remained unchanged. It is inferred that DJ-1 likely exerts in the retina a potential neuroprotective role against oxidative stress, including alpha-synuclein oxidation and aggregation, which should be operative under both physiological and pathological conditions.