Open AccessPhosphatidylglycerol Incorporates into Cardiolipin to Improve Mitochondrial Activity and Inhibits Inflammation
Author(s) -
Weiwei Chen,
Yu-Jen Chao,
Wan-Hsin Chang,
Jui-Fen Chan,
Yuan-Hao Hsu
Publication year - 2018
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-018-23190-z
Subject(s) - cardiolipin , downregulation and upregulation , phospholipid scramblase , chemistry , inflammation , mitochondrion , inner mitochondrial membrane , phosphatidylglycerol , sod2 , biochemistry , oxidative stress , microbiology and biotechnology , phospholipid , biology , superoxide dismutase , phosphatidylserine , gene , immunology , membrane , phosphatidylcholine
Chronic inflammation and concomitant oxidative stress can induce mitochondrial dysfunction due to cardiolipin (CL) abnormalities in the mitochondrial inner membrane. To examine the responses of mitochondria to inflammation, macrophage-like RAW264.7 cells were activated by Kdo2-Lipid A (KLA) in our inflammation model, and then the mitochondrial CL profile, mitochondrial activity, and the mRNA expression of CL metabolism-related genes were examined. The results demonstrated that KLA activation caused CL desaturation and the partial loss of mitochondrial activity. KLA activation also induced the gene upregulation of cyclooxygenase (COX)-2 and phospholipid scramblase 3, and the gene downregulation of COX-1, lipoxygenase 5, and Δ-6 desaturase. We further examined the phophatidylglycerol (PG) inhibition effects on inflammation. PG supplementation resulted in a 358-fold inhibition of COX-2 mRNA expression. PG(18:1) 2 and PG(18:2) 2 were incorporated into CLs to considerably alter the CL profile. The decreased CL and increased monolysocardiolipin (MLCL) quantity resulted in a reduced CL/MLCL ratio. KLA-activated macrophages responded differentially to PG(18:1) 2 and PG(18:2) 2 supplementation. Specifically, PG(18:1) 2 induced less changes in the CL/MLCL ratio than did PG(18:2) 2 , which resulted in a 50% reduction in the CL/MLCL ratio. However, both PG types rescued 20–30% of the mitochondrial activity that had been affected by KLA activation.