title: [Inactivation of p53 leads to enhancement of tyrosine hydroxylase biosynthesis in the dopaminergic brain neurons].
abstract: In the present work we analyzed a possibility of interaction of protein p53, family members of the ERK1/2 signaling cascade, and the transcription factor CREB in regulation of functional activity of dopaminergic neurons. There were considered neurons of Substantia nigra and Zona incerta of control rats and of rats injected intraperitoneally with chemical inhibitor of p53 Pifithrin-alpha blocking transcription activity ofproapoptotic protein p53. We have shown the p53 inactivation to lead to an increase in the content of tyrosine'hydroxylase both in cell bodies and in terminal parts of axons. At the same time, activity of the transcription factor CREB is enhanced in the brain dopaminergic neurons. No significant differences in the content of phospho-ERK1/2 kinases were revealed in the cell bodies at use of Pifithrin-alpha as compared with control group. Thus, we have shown that action of p53 on biosynthesis of tyrosine hydroxylase is of inhibitory character and seems to be mediated by the transcription factor CREB.
authors.forename: N A
authors.initials: NA
authors.lastname: Dorofeeva
authors.forename: L S
authors.initials: LS
authors.lastname: Nikitina
authors.forename: M V
authors.initials: MV
authors.lastname: Glazova
authors.forename: O D
authors.initials: OD
authors.lastname: Kirillova
authors.forename: E V
authors.initials: EV
authors.lastname: Chernigovskaia
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003627:Data Interpretation, Statistical; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020530:Subthalamus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014050:Toluene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
chemical_list: D052160:Benzothiazoles; D017362:Cyclic AMP Response Element-Binding Protein; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin; D014446:Tyrosine 3-Monooxygenase