Oxidative stress‐mediated down‐regulation of bcl‐2 promoter in hippocampal neurons

• DOI: 10.1046/j.1471-4159.2003.01606.x
• Publication Date: 2003-03-12T07:04:25Z
• Authors: Subbiah Pugazhenthi; Albina Nesterova; Purevsuren Jambal; Gerald Audesirk; Marcey Kern; Leigh Cabell; Eva Eves; Marsha R. Rosner; Linda M. Boxer; Jane E.‐B. Reusch
• Keywords: Neurons; 0303 health sciences; Cell Survival; Down-Regulation; Oxidants; Hippocampus; Cell Line; Rats; Rats, Sprague-Dawley; Glucose Oxidase; Oxidative Stress; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Animals; Fibroblast Growth Factor 2; RNA, Messenger; Cyclic AMP Response Element-Binding Protein; Promoter Regions, Genetic; Cells, Cultured

Abstract Generation of oxidative stress/reactive oxygen species (ROS) is one the causes neuronal apoptosis. We have examined effects ROS at transcriptional level in an immortalized hippocampal cell line (H19‐7) and rat primary neurons. Treatment H19‐7 cells with hydrogen peroxide (150 µ m ) resulted a 40% decrease Bcl‐2 protein parallel bcl‐2 mRNA levels. overexpressing were found to be resistant ROS‐induced had previously shown that promoter activity positively regulated by transcription factor cyclic AMP response element binding (CREB) In present study, we demonstrate decreases luciferase reporter gene driven site containing promoter. Exposure neurons for 6 h basal fibroblast growth factor‐2‐stimulated phosphorylation/activation CREB. Chronic 24 treatment led significant ( p < 0.01) CREB Adenoviral overexpression wild type protection against apoptosis through up‐regulation expression whereas dominant negative exaggerated injury. These findings loss function contributes stress‐induced dysfunction.