RRC ID 59656
Author Youssef M, Ibrahim A, Akashi K, Hossain MS.
Title PUFA-Plasmalogens Attenuate the LPS-Induced Nitric Oxide Production by Inhibiting the NF-kB, p38 MAPK and JNK Pathways in Microglial Cells.
Journal Neuroscience
Abstract The special lipids plasmalogens (Pls) were reported to be reduced in the neurodegenerative brains such as Alzheimer's disease where a marked increase of glial activation is often observed. We previously found that a reduction of brain Pls can enhance the glial activation in murine brains. However, the detailed role of Pls in the prevention of glial activation was mostly elusive. Here we report that the Pls, extracted from scallop (sPls), significantly inhibited the inducible form of nitric oxide synthase (NOS2) and the production of NO in LPS (lipopolysaccharide)-activated microglial cells. We also observed that the polyunsaturated docosahexaenoic acid (DHA)-containing Pls but not the monounsaturated oleic acid-containing Pls attenuated the NOS2 induction. In addition, sPls blocked the activation of nuclear factor (NF)-kB and mitogen-activated protein kinases (MAPKs) e.g., JNK and p38 MAPK, thereby attenuated the nuclear translocation of NF-kB subunit, p65, and activator protein-1 (AP-1) proteins (c-Fos and c-Jun). Interestingly, LPS treatments suppressed the expression of Pls synthesizing enzymes, glycerone phosphate O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the microglial cells by the p38MAPK and JNK pathways. Furthermore, the knockdown of GNPAT and AGPS genes by sh-RNAs accelerated the LPS-induced activation of p38MAPK and JNK, resulting in the increased production of NO. These findings suggested that a decrease of brain Pls can activate the NF-kB, p38MAPK and JNK pathways to induce a prolonged microglial activation which may downplay the neuroprotective events in the brains of neurodegenerative diseases.
Volume 397
Pages 18-30
Published 2019-1-15
DOI 10.1016/j.neuroscience.2018.11.030
PII S0306-4522(18)30763-2
PMID 30496826
MeSH Animals Cell Line Fatty Acids, Unsaturated / metabolism* JNK Mitogen-Activated Protein Kinases / metabolism Lipopolysaccharides Mice Microglia / enzymology* Microglia / immunology* Mitogen-Activated Protein Kinases / metabolism NF-kappa B / metabolism Nitric Oxide / metabolism* Nitric Oxide Synthase Type II / metabolism Plasmalogens / metabolism* RNA, Messenger / metabolism Signal Transduction
IF 3.244
Times Cited 10
Human and Animal Cells MG6(RCB2403)