Palmitic acid methyl ester inhibits cardiac arrest-induced neuroinflammation and mitochondrial dysfunction.
Animals
Calcium-Binding Proteins
/ metabolism
Cardiopulmonary Resuscitation
Cerebrovascular Circulation
/ drug effects
Cytokines
Disease Models, Animal
Heart Arrest
/ drug therapy
Hippocampus
/ drug effects
Male
Membrane Proteins
/ metabolism
Microfilament Proteins
/ metabolism
Mitochondria
/ drug effects
Neuroprotective Agents
/ administration & dosage
Oxygen Consumption
Palmitates
/ administration & dosage
Protein-Arginine N-Methyltransferases
/ metabolism
Rats
Rats, Sprague-Dawley
Repressor Proteins
/ metabolism
Asphyxial cardiac arrest
Mitochondrial function
Neuroinflammation
Oxygen consumption rate
Palmitic acid methyl ester
Protein arginine methyltransferase
Journal
Prostaglandins, leukotrienes, and essential fatty acids
ISSN: 1532-2823
Titre abrégé: Prostaglandins Leukot Essent Fatty Acids
Pays: Scotland
ID NLM: 8802730
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
31
08
2020
revised:
15
12
2020
accepted:
15
12
2020
pubmed:
15
1
2021
medline:
1
12
2021
entrez:
14
1
2021
Statut:
ppublish
Résumé
We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator released from the sympathetic ganglion with vasoactive properties. Post-treatment with PAME can enhance cortical cerebral blood flow and functional learning and memory, while inhibiting neuronal cell death in the CA1 region of the hippocampus under pathological conditions (i.e. cerebral ischemia). Since mechanisms underlying PAME-mediated neuroprotection remain unclear, we investigated the possible neuroprotective mechanisms of PAME after 6 min of asphyxial cardiac arrest (ACA, an animal model of global cerebral ischemia). Our results from capillary-based immunoassay (for the detection of proteins) and cytokine array suggest that PAME (0.02 mg/kg) can decrease neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) and inflammatory cytokines after cardiopulmonary resuscitation. Additionally, the mitochondrial oxygen consumption rate (OCR) and respiratory function in the hippocampal slices were restored following ACA (via Seahorse XF24 Extracellular Flux Analyzer) suggesting that PAME can ameliorate mitochondrial dysfunction. Finally, hippocampal protein arginine methyltransferase 1 (PRMT1) and PRMT8 are enhanced in the presence of PAME to suggest a possible pathway of methylated fatty acids to modulate arginine-based enzymatic methylation. Altogether, our findings suggest that PAME can provide neuroprotection in the presence of ACA to alleviate neuroinflammation and ameliorate mitochondrial dysfunction.
Identifiants
pubmed: 33445063
pii: S0952-3278(20)30185-X
doi: 10.1016/j.plefa.2020.102227
pmc: PMC8174449
mid: NIHMS1661898
pii:
doi:
Substances chimiques
Aif1 protein, rat
0
Calcium-Binding Proteins
0
Cytokines
0
Membrane Proteins
0
Microfilament Proteins
0
Neuroprotective Agents
0
Palmitates
0
Repressor Proteins
0
methyl palmitate
DPY8VCM98I
PRMT1 protein, human
EC 2.1.1.319
PRMT8 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102227Subventions
Organisme : NINDS NIH HHS
ID : R01 NS096225
Pays : United States
Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
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