title: Lipidomic analysis of molecular cardiolipin species in livers exposed to ischemia/reperfusion.
abstract: Transient hepatic ischemia can cause significant liver injury. A central and early event in ischemia/reperfusion (I/R) injury is the impairment of mitochondria. The phospholipid cardiolipin (CL) is required for efficient mitochondrial function. The aim of this study was to analyze composition, content, and oxidation of CL in dependence of I/R stress. Therefore, we exposed rat livers to 20 min ischemia by interrupting the perfusion with Krebs-Ringer solution in situ. Tissue histology as well as increased activities of LDH, GLDH, and ASAT analysed in the efflux after 50 min reperfusion indicated impairment of the liver. For the analysis of local CL distribution the liver homogenate was separated according to density into 11 fractions. The fractions displayed different contents of CL and citrate synthase peaking at density of about 1.07 g/cm(3). Among the fractions, the distribution of molecular CL species significantly differed. I/R caused loss of about 30 % CL and 17 % citrate synthase activity. Further, I/R shifted the CL and citrate synthase activity profile toward lower densities. Oxidized CL was exclusively found in fractions with high CL and citrate synthase content after I/R stress. I/R treatment caused significant changes in the distribution of molecular CL species. Our data demonstrate that I/R causes significant decrease in CL content and increase of oxidized CL that may be of impact for impairment of mitochondrial function by I/R. These results lead to the suggestion that strategies supporting anti-oxidative defence and CL synthesis may be beneficial to reduce I/R injury of the liver.
authors.affiliation: Department of Pathological Biochemistry, Medical Faculty, Institute of Clinical Chemistry and Pathological Biochemistry, Otto-von-Guericke-University, Magdeburg, Leipziger Str. 44, Magdeburg, Germany.
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Martens
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Walter
authors.initials: W
authors.lastname: Halangk
authors.forename: Thomas
authors.initials: T
authors.lastname: Wartmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Gardemann
authors.forename: Ilona
authors.initials: I
authors.lastname: Päge
authors.forename: Lorenz
authors.initials: L
authors.lastname: Schild
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
chemical_list: D002308:Cardiolipins; D010743:Phospholipids; D002950:Citrate (si)-Synthase