Premium
A transcriptomic approach to the survival signaling enhanced by Neuroprotectin D1 in response to oxidative stress
Author(s) -
Calandria Jorgelina M,
Bazan Nicolas G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb266
Subject(s) - gene knockdown , transcriptome , microbiology and biotechnology , oxidative stress , signal transduction , biology , gene expression , transcription factor , mapk/erk pathway , microarray analysis techniques , chemokine , transcriptional regulation , regulation of gene expression , apoptosis , gene , inflammation , immunology , biochemistry
Oxidative stress triggers apoptotic damage on RPE cells, enhancing the enzymatic production of neuroprotectin D1 (NPD1) that down‐regulates the expression of pro‐inflammatory enhancing the expression of the anti‐apoptotic proteins. We hypothesize that NPD1 signaling promotes the modulation of a group of genes that contributes to the homeostatic survival response of RPE cells. 15LOX1 knockdown cells were used to study the NPD1‐dependent transcriptional control. The oxidative stress‐induced expression in the silenced cells and controls with and without NPD1 was assessed by microarray technology. To construct the NPD1‐transcriptome, enrichment analysis was used to identify the over‐represented genes for common, similar and unique sets. Functional ontologies, Gene Go and GO cellular processes were applied. More than 300 genes were shown to be modulated in response to NPD1. Chemokines such as pro‐mitotic CXCL1 were down‐regulated by 6 hs of oxidative stress and up‐regulated by NPD1, and CXCL3 was down‐regulated by NPD1. The expression of transcriptional regulators was observed at early times of oxidative stress treatment. MAPK pathway components also were modulated by NPD1. The transcription factor network analysis showed the involvement of NF‐kB, c‐Jun and EGR1 among others. Different cellular processes were affected by NPD1 treatment involving stress and immune response signaling via MAPK. The data suggests that NPD1 induce the modification of gene expression, enhancing the intrinsic pathways related with RPE cell survival regulation. (NIH/NEI Grant EY005121).