Oxygen-glucose-deprived rat primary neural cells exhibit DJ-1 translocation into healthy mitochondria: a potent stroke therapeutic target.

AIMS: DJ-1 is a key redox-reactive neuroprotective protein implicated in regulation of oxidative stress after stroke. However, the molecular mechanism, especially the role of mitochondrial function, by which DJ-1 protects neural cells in stroke remains to be elucidated. The aim of this study was to reveal whether DJ-1 translocates into the mitochondria in exerting neuroprotection against oxidative stress. In particular, we examined DJ-1 secretion from primary rat neural cells (PRNCs) exposed to experimental stroke.

METHODS

Primary rat neural cells were exposed to the oxygen-glucose deprivation (OGD), an established in vitro stroke model, and DJ-1 translocation was measured by immunocytochemistry, and its secretion detected by ELISA.

RESULTS

Under OGD, DJ-1 translocated into the healthy mitochondria, and significant levels of DJ-1 protein were detected. Treatment with anti-DJ-1 antibody reduced cell viability and mitochondrial activity, and increased glutathione level. Interestingly, OGD reversed the ratio of astrocyte/neuron cells (6/4 to 4/6).

CONCLUSIONS

Altogether, these results revealed that DJ-1 participates in the acute endogenous neuroprotection after stroke via the mitochondrial pathway. That DJ-1 was detected immediately after stroke and efficiently translocated into the mitochondria offer a new venue for developing neuroprotective and/or neurorestorative strategies against ischemic stroke.