Monolyso-cardiolipin-biomarker of mitochondrial dysfunction induced by total body irradiation. LC-ESI-MS Study.
Tyurin-VA; Zhao-H; Tyurina-Y; Epperly-MW; Greenberger-JS; Kagan-VE
Toxicologist 2012 Mar; 126(Suppl 1):438
Oxidized phospholipids and their hydrolysis products are important signaling participants of the mitochondrial stage of apoptosis. Although cardiolipin (CL) comprises a minor fraction of cell phospholipids, its regulatory function is central to cell activity. Previously, we demonstrated that total body irradiation (TBI) results in oxidation of CL in small intestine and lung. Characterization of individual oxidized molecular species of CL and their hydrolysis products is essential for further understanding of mechanisms of radiation damage and development of radioprotectors/ radiomitigators. C57BL6 mice were exposed to TBI at a dose of 10 Gy and sacrificed 0, 10 and 24 h thereafter. Oxidative lipidomics analysis of CL and its hydrolysis products isolated from lung, brain, bone marrow, small intestine and plasma was preformed. We found that TBI results in significantly decreased content of CL in small intestine, bone marrow (5.3- and 2.4-times, respectively) compared to lung and brain tissues. We were able to detect a significant accumulation of nonoxidized monolyso-CL (MCL) in tissues from irradiated mice. In addition, we found that MCL was a major CL hydrolysis product containing exclusively linoleic acid. Moreover, a significant increase of CL molecular species containing four linoleic acids (m/z 1448) was found in plasma of mice 10 h after TBI. We suggest that appearance of mitochondrial phospholipid, CL, and its metabolites in plasma of irradiated mice may reflect tissue-specific irradiation-induced metabolic disturbances and serve as biomarkers of mitochondrial dysfunction induced by TBI.
Phospholipids; Oxidative-phosphorylation; Oxidative-processes; Oxidation; Cellular-function; Cell-morphology; Irradiation; Oxidation; Intestinal-cells; Lung-cells; Radiation; Radiation-injury; Laboratory-animals; Laboratory-testing; Bone-marrow; Brain-matter; Tissue-culture; Biochemical-indicators; Biomarkers; Metabolites
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
University of Pittsburgh at Pittsburgh