title: Cell density increases Bcl-2 and Bcl-x expression in addition to survival of cultured cerebellar granule neurons.
abstract: The proto-oncogene bcl-2 and its family members, bcl-x and bax are recognized as major regulators of cell death and survival. Although Bcl-2 and Bcl-x are expressed in brain, little is known how they are regulated in neurons. Here we have studied the expression of bcl-2, bcl-xL and bax mRNA in rat cerebellar granule neurons cultured under conditions which influence neuron survival. Insulin-like growth factor-1 and brain-derived neurotrophic factor supported the survival of these neurons, but affected neither the expression of bcl-2, bcl-xL nor bax mRNA. In contrast, bcl-2 and bcl-xL mRNAs were up-regulated in cerebellar granule neurons plated at high density exhibiting an increased neuronal survival. Western blots showed that cell density also increased Bcl-2 protein level. However, conditioned medium from dense cultures did not affect the level of bcl-2 mRNA nor survival of the neurons. This suggests that cell density promotes survival and regulates Bcl-2 expression in cerebellar granule neurons through a signaling pathway different from known neurotrophic factors.
authors.affiliation: Department of Neurochemistry, Max Planck Institute for Psychiatry, Planegg-Martinsried, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohga
authors.forename: U
authors.initials: U
authors.lastname: Zirrgiebel
authors.forename: S
authors.initials: S
authors.lastname: Hamnér
authors.forename: T M
authors.initials: TM
authors.lastname: Michaelidis
authors.forename: J
authors.initials: J
authors.lastname: Cooper
authors.forename: H
authors.initials: H
authors.lastname: Thoenen
authors.forename: D
authors.initials: D
authors.lastname: Lindholm
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D015870:Gene Expression; D019254:Genes, bcl-2; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D007334:Insulin-Like Growth Factor I