Modulation of transcription factor Nrf2 in an in vitro model of traumatic brain injury.
Traumatic brain injury (TBI) afflicts approximately 1.4 million people in the United States and TBIs have been labeled a major cause of death and disability on a global scale. Regulatory responses in a variety of neuronal loss conditions have supported the protective involvement of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor. Nrf2 regulates antioxidant enzyme genes, and an increase in Nrf2 expression may counteract oxidative damage that results from TBI. Elevated Nrf2 may ultimately act through the upregulation of downstream target genes such as thioredoxin (Trx) and heat-shock protein-70 (HSP70) and this may reduce neuronal loss. We performed multiple mild biaxial stretch injuries to neuroblastoma cells in culture, and examined the effects of the Nrf2 activator, tert-butylhydroquinone (tBHQ). We also compared the stretch injury to oxidative insult. We confirmed that Trx and HSP70 were upregulated by treatment with tBHQ. We observed that tBHQ protected neurons from either insult, and that this was evident by different measures of cell viability and a decrease in annexin V binding. Neuronal health after insult was improved approximately 50% by tBHQ, indicating that neurons exposed to TBI in vitro can be protected.
Laboratory of Molecular Biology, Research and Development 151, Bay Pines VA Healthcare System, Bay Pines, Florida 33744-4125, USA.
Haris
H
Hatic
Michael J
MJ
Kane
Jessica N
JN
Saykally
Bruce A
BA
Citron
D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007150:Immunohistochemistry; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000096:biosynthesis
D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013879:Thioredoxins; C018855:2-tert-butylhydroquinone