Induction of Serpinb1a by PACAP or NGF is Required for PC12 Cells Survival After Serum Withdrawal

Overview

Journal J Neurochem

Specialties Chemistry
Neurology

Date 2014 Jun 6

PMID 24899316

Citations 8

Authors

Tommy Seaborn

Aurelia Ravni

Ruby Au

Bill K C Chow

Alain Fournier

Olivier Wurtz

Hubert Vaudry

Lee E Eiden

David Vaudry

Affiliations

Soon will be listed here.

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.

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