Oxygen–Glucose‐Deprived Rat Primary Neural Cells Exhibit DJ‐1 Translocation into Healthy Mitochondria: A Potent Stroke Therapeutic Target

Abstract

SummaryAims 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.MethodsPrimary 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.ResultsUnder 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).ConclusionsAltogether, 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.