Phosphatidylglycerols Induce the Changes of Cardiolipin Composition and Mitochondrial Functions during Inflammation

• Main Authors: CHEN, WEI-WEI, 陳韋維
• Other Authors: HSU,YUAN-HAO
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/67395240777228389376

碩士 === 東海大學 === 化學系 === 104 === Macrophages are activaed by inflammatory agent that cause inflammation.The primary cells of chronic inflammatory are macrophages when acute inflammation is not resolved. Chronic inflammation and oxidative stress induce mitochondrial dysfunction. Cardiolipin (CL) oxidation during electron transport chain abnormalities at mitochondrial inner membrane. Phophatidylglycerol (PG) synthesized CL also inhibit inflammation of macrophage. This experiment studies that PG regulate CL composition and mitochondrial function. We examined the changes of mRNA expression of mitochondrial related protein by RT-qPCR, CL and monolyso-cardiolipin (MLCL) species by LC-MS and the mitochondrial activity by seahorse XF analyzer while RAW264.7 cells treated with PG(18:1)2 and PG(18:2)2. Our results display the RAW264.7 treated with different species of PG can regulate the acyl chain in CL. And the ratio of CL/MLCL decreased from 25 fold to 10 fold suggesting the CL quantity decreased and MLCL quantity increased in a cell. The RAWcell treated with PG(18:1)2 did not obvious change at the mitochondrial activity, but decreased in PG(18:2)2 treated. Activated macrophages by Kdo2-Lipid A (KLA) reduced the degree of unsaturation on CL acyl chain, and decreased at the mitochondrial activity. The cardiolipin and MLCL quantity didn’t change during macrophages activated. Interestingly, the degree of unsaturation of CL didn’t affect while both species of PG treated with macrophages before KLA added, and improved the activity of mitochondria during cells activated. Overall, the unsaturation of CL acyl chain can be transformed by different degree of unsaturation species of PG. The mRNA expression showed the PG treated cells changed the CL quantity and composition by reducing the efficacy of lysocardiolipin acyltransferase and δ-6-desaturase. Macrophage activation reduced the degree of CL unsaturation by decreasing the level of CL remodeling enzymes. PG inhibited the COX-2 induced inflammation, and it maintained the level of mitochondrial respiration during the macrophage activated.