title: Induction of serpinb1a by PACAP or NGF is required for PC12 cells survival after serum withdrawal.
abstract: PC12 cells are used to study the signaling mechanisms underlying the neurotrophic and neuroprotective activities of pituitary adenylate cyclase-activating polypeptide (PACAP) and nerve growth factor (NGF). Previous microarray experiments indicated that serpinb1a was the most induced gene after 6 h of treatment with PACAP or NGF. This study confirmed that serpinb1a is strongly activated by PACAP and NGF in a time-dependent manner with a maximum induction (~ 50-fold over control) observed after 6 h of treatment. Co-incubation with PACAP and NGF resulted in a synergistic up-regulation of serpinb1a expression (200-fold over control), suggesting that PACAP and NGF act through complementary mechanisms. Consistently, PACAP-induced serpinb1a expression was not blocked by TrkA receptor inhibition. Nevertheless, the stimulation of serpinb1a expression by PACAP and NGF was significantly reduced in the presence of extracellular signal-regulated kinase, calcineurin, protein kinase A, p38, and PI3K inhibitors, indicating that the two trophic factors share some common pathways in the regulation of serpinb1a. Finally, functional investigations conducted with siRNA revealed that serpinb1a is not involved in the effects of PACAP and NGF on PC12 cell neuritogenesis, proliferation or body cell volume but mediates their ability to block caspases 3/7 activity and to promote PC12 cell survival.
authors.affiliation: Neurotrophic Factor and Neuronal Differentiation Team, Inserm U982, DC2N, Mont-Saint-Aignan, France; International Associated Laboratory Samuel de Champlain, Mont-Saint-Aignan, France; Department of Pediatrics, Hôpital St-François d'Assise, Centre de Recherche du Centre Hospitalier Universitaire de Québec (CRCHUQ), Laval University, Québec, Canada.
authors.forename: Tommy
authors.initials: T
authors.lastname: Seaborn
authors.forename: Aurélia
authors.initials: A
authors.lastname: Ravni
authors.forename: Ruby
authors.initials: R
authors.lastname: Au
authors.forename: Bill K C
authors.initials: BK
authors.lastname: Chow
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Olivier
authors.initials: O
authors.lastname: Wurtz
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D015843:Serpins / Q000096:biosynthesis*
chemical_list: D016895:Culture Media, Serum-Free; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C522950:Serpinb1a protein, mouse; D015843:Serpins; D020932:Nerve Growth Factor
keywords: caspase; cell death; cell survival; nerve growth factor; neuroprotection; pituitary adenylate cyclase-activating polypeptide