Phosphatidylglycerol Incorporates into Cardiolipin to Improve Mitochondrial Activity and Inhibits Inflammation.

Abstract

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.

• Authors: Wei-Wei Chen, Yu-Jen Chao, Wan-Hsin Chang, Jui-Fen Chan, Yuan-Hao Howard Hsu
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 4919 (03 20 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29559686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiolipins
• Kdo2-lipid A
• Lipopolysaccharides
• Lysophospholipids
• Phosphatidylglycerols
• monolysocardiolipin
• Cyclooxygenase 2

Topics

• Animals
• Cardiolipins (metabolism)
• Cyclooxygenase 2 (genetics, metabolism)
• Gene Expression Regulation
• Inflammation (metabolism)
• Lipopolysaccharides (metabolism)
• Lysophospholipids (metabolism)
• Macrophage Activation
• Macrophages (physiology)
• Mice
• Mitochondria (metabolism)
• Mitochondrial Membranes (metabolism)
• Phosphatidylglycerols (metabolism)
• RAW 264.7 Cells