title: Neurturin suppresses injury-induced neuronal activating transcription factor 3 expression in cultured guinea pig cardiac ganglia.
abstract: Cultured guinea pig atrial whole mounts containing the intrinsic cardiac ganglia were used as an in vitro model to investigate the induction of the stress/injury marker activating transcription factor 3 (ATF-3). ATF-3 expression was quantified by using immunocytochemical labeling and real-time PCR. In freshly isolated ganglia, no neuronal or Schwann cell nuclei exhibited ATF-3 immunoreactivity. In 2-hour cultures, the induction of ATF-3 expression was evident in many Schwann cell nuclei, whereas no neuronal nuclei were ATF-3 immunoreactive. Beginning at 4 hours, the percentage of neurons with ATF-3-immunoreactive nuclei increased progressively, and, by 48 hours in culture, approximately 95% of the cardiac neurons had ATF-3-immunoreactive nuclei. Neurturin significantly suppressed ATF-3 expression in 48-hour-cultured neurons without effect on ATF-3 expression in Schwann cell nuclei. Neuturin also could reverse neuronal ATF-3 expression after its induction. The suppression of ATF-3 induction by neurturin was mediated by activation of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Glial-derived neurotrophic factor (GDNF) also suppressed neuronal ATF-3 induction during culture. However, culture in serum-free media, presence of nerve growth factor, or addition of pituitary adenylate cyclase-activating polypeptide had no effect on ATF-3 induction in the 48-hour-cultured cardiac neurons. By 4 hours in culture, there was a significant increase in ATF-3 transcript levels, and neurturin partially suppressed ATF-3 transcript levels in 48-hour cultures. It is proposed that the loss of target-derived neurturin is a potential mechanism stimulating injury-induced expression of ATF-3 in cardiac neurons.
authors.affiliation: Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Young
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Girard
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Parsons
mesh_terms: D051700:Activating Transcription Factor 3 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000293:injuries* / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051101:Neurturin / Q000494:pharmacology* / Q000502:physiology
chemical_list: D051700:Activating Transcription Factor 3; D051101:Neurturin