DJ-1 ameliorates ischemic cell death in vitro possibly via mitochondrial pathway.
DJ-1 is an important redox-reactive neuroprotective protein implicated in regulation of oxidative stress after ischemia. However the molecular mechanism, especially the mitochondrial function, by which DJ-1 protects neuronal 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 an in vitro model of stroke. Human neural progenitor cells (hNPCs) were initially exposed to oxygen-glucose deprivation and reperfusion injury, and thereafter, DJ-1 translocation was measured by immunocytochemistry and its secretion by hNPCs was detected by enzyme-linked immunosorbant assay (ELISA). Exposure of hNPCs to experimental stroke injury resulted in DJ-1 translocation into the mitochondria. Moreover, significant levels of DJ-1 protein were secreted by the injured hNPCs. Our findings revealed that DJ-1 principally participates in the early phase of stroke involving the mitochondrial pathway. DJ-1 was detected immediately after stroke and efficiently translocated into the mitochondria offering a new venue for developing treatment strategies against ischemic stroke.
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, USA.
Yuji
Y
Kaneko
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, USA; Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan.
Hideki
H
Shojo
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, USA.
Jack
J
Burns
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, USA.
Meaghan
M
Staples
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, USA; School of Physical Therapy & Rehabilitation Sciences, University of South Florida Morsani College of Medicine, USA.
Naoki
N
Tajiri
Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, USA. Electronic address: cborlong@health.usf.edu.
Cesar V
CV
Borlongan
D016923:Cell Death; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
Cell death; Mitochondria; Neuroprotection; Stem cells; Stroke