NPD1-mediated stereoselective regulation of BIRC3 expression through cREL is decisive for neural cell survival.

Abstract

Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived mediator, induces cell survival in uncompensated oxidative stress (OS), neurodegenerations or ischemic stroke. The molecular principles underlying this protection remain unresolved. We report here that, in retinal pigment epithelial cells, NPD1 induces nuclear translocation and cREL synthesis that, in turn, mediates BIRC3 transcription. NPD1 activates NF-κB by an alternate route to canonical signaling, so the opposing effects of TNFR1 and NPD1 on BIRC3 expression are not due to interaction/s between NF-κB pathways. RelB expression follows a similar pattern as BIRC3, indicating that NPD1 also is required to activate cREL-mediated RelB expression. These results suggest that cREL, which follows a periodic pattern augmented by the lipid mediator, regulates a cluster of NPD1-dependent genes after cREL nuclear translocation. BIRC3 silencing prevents NPD1 induction of survival against OS. Moreover, brain NPD1 biosynthesis and selective neuronal BIRC3 abundance are increased by DHA after experimental ischemic stroke followed by remarkable neurological recovery. Thus, NPD1 bioactivity governs key counter-regulatory gene transcription decisive for retinal and brain neural cell integrity when confronted with potential disruptions of homeostasis.

• Authors: J M Calandria, A Asatryan, V Balaszczuk, E J Knott, B K Jun, P K Mukherjee, L Belayev, N G Bazan
• Journal: Cell death and differentiation (Cell Death Differ) Vol. 22 Issue 8 Pg. 1363-77 (Aug 2015) ISSN: 1476-5403 [Electronic] England
• PMID: 25633199 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inhibitor of Apoptosis Proteins
• Proto-Oncogene Proteins c-rel
• protectin D1
• Transcription Factor RelB
• Docosahexaenoic Acids
• BIRC3 protein, human
• Baculoviral IAP Repeat-Containing 3 Protein
• Ubiquitin-Protein Ligases

Topics

• Baculoviral IAP Repeat-Containing 3 Protein
• Cell Survival (drug effects, genetics)
• Cells, Cultured
• Docosahexaenoic Acids (pharmacology)
• Humans
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• Oxidative Stress (drug effects, genetics)
• Proto-Oncogene Proteins c-rel (metabolism)
• Signal Transduction (drug effects)
• Transcription Factor RelB (genetics, metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)