Dépôt numérique

Induction of serpinb1a by PACAP or NGF is required for PC12 cells survival after serum withdrawal

Seaborn, Tommy; Ravni, Aurélia; Au, Ruby; Chow, Bill K.C.; Fournier, Alain; Wurtz, Olivier; Vaudry, Hubert; Eiden, Lee E. et Vaudry, David (2014). Induction of serpinb1a by PACAP or NGF is required for PC12 cells survival after serum withdrawal Journal of Neurochemistry , vol. 131 , nº 1. pp. 21-32. DOI: 10.1111/jnc.12780.

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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 6h 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 (similar to 50-fold over control) observed after 6h 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.

Type de document: Article
Mots-clés libres: caspase; cell death; cell survival; nerve growth factor; neuroprotection; pituitary adenylate cyclase-activating polypeptide
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 21 sept. 2017 19:27
Dernière modification: 10 mai 2021 19:06
URI: https://espace.inrs.ca/id/eprint/3110

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