title: Cocaine induces ubiquitination of Egr-1 in the rat dorsal striatum.
abstract: Early growth response (Egr) is a member of the zinc finger family of transcription factors that reflects neuronal activity induced by various stimuli. Acute cocaine administration elicits rapid and transient induction of several immediate early genes in brain neurons. However, the mechanism regulating the degradation of the Egr-1 protein is not clearly understood. In this study, rats were injected with cocaine and the relationships among locomotor activity, Egr-1 protein level, phosphorylation of upstream kinase extracellular regulated kinase (ERK)1/2, Egr-1 mRNA expression, and ubiquitination of the Egr-1 protein were measured in the dorsal striatum and the frontal cortex. Locomotor activity reached a peak at about 15 min, and phosphorylation of ERK1/2 and Egr-1 mRNA level also increased at that time. However, the Egr-1 protein level decreased initially in the dorsal striatum, probably due to ubiquitination-mediated degradation. When locomotor activity decreased substantially at 30 min, the phosphorylation of ERKs and expression levels of Egr-1 mRNA and protein reached their peak levels and the protein level subsequently increased. These findings indicate that immediate early gene protein levels would not be a reliable indicator of increased regional activity in the brain. Thus, observations spanning multiple time periods or the examination of mRNA rather than protein would be recommended in these situations.
authors.affiliation: aClinical Research Institute, Seoul National University Hospital bInstitute of Human Behavioral Medicine cDepartment of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Shijie
authors.initials: S
authors.lastname: Xu
authors.forename: Ung Gu
authors.initials: UG
authors.lastname: Kang
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003042:Cocaine