Ischemia In Vivo Induces Cardiolipin Oxidation in Rat Kidney Mitochondria

Abstract

Cardiolipin is a mitochondrial phospholipid that plays a significant role in mitochondrial bioenergetics. Cardiolipin is oxidized under conditions like oxidative stress that occurs during ischemia/reperfusion; however, it is known that even during ischemia, many reactive oxygen species are generated. Our aim was to analyze the effect of in vivo ischemia on cardiolipin oxidation. Adult male Wistar rats were anesthetized; then, their abdomens were opened, and microvascular clips were placed on renal arteries for 30, 40 or 60 min, causing ischemia. After ischemia, kidneys were harvested, mitochondria were isolated, and lipids were extracted for chromatographic and mass spectrometric analysis of tetralinoleoyl cardiolipin and its oxidation products. Chromatographic and mass spectrometric analysis revealed a 47%, 68% and 74% decrease in tetralinoleoyl cardiolipin after 30 min, 40 min and 60 min of renal ischemia, respectively (p < 0.05). Eight different cardiolipin oxidation products with up to eight additional oxygens were identified in rat kidney mitochondria. A total of 40 min of ischemia caused an average of a 6.9-fold increase in all oxidized cardiolipin forms. We present evidence that renal ischemia in vivo alone induces tetralinoleoyl cardiolipin oxidation and depletion in rat kidney mitochondria.

Mn(III) Porphyrin, MnTnBuOE-2-PyP5+, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress

“…Cardiolipins are highly susceptible to oxidation because of their unique location near the site of ROS generation and the presence of unsaturated fatty acids [ 39 , 41 ]. Several studies have shown that peroxidation of cardiolipin increases following ischemia/reperfusion injury [ 42 , 43 ]. In line with the previous results, our study demonstrated that cardiolipin peroxidation increases following H/R injury in H9c2 cardiomyocytes, and BMX-001 protects cardiolipin against oxidation.…”

In Vitro Hypoxia/Reoxygenation Induces Mitochondrial Cardiolipin Remodeling in Human Kidney Cells

“…Separation and investigation of individual cardiolipin forms was performed by ultra-effective liquid chromatography—tandem mass spectrometry (UPLC-MS/MS) using Waters Acquity UPLC chromatography system coupled with a Xevo TQD (triple quadrupole) mass spectrometer (Waters, Milford, MA, USA) as described before [ 60 ]. Data was analyzed using MassLynx V4.1.…”

Cyclohexylalanine-Containing α-Helical Amphipathic Peptide Targets Cardiolipin, Rescuing Mitochondrial Dysfunction in Kidney Injury

“…Mitochondrial dysfunction, caused by DNA damage or environmental stresses, leads to intrinsic mitochondrial diseases and degenerative diseases. , Cardiolipin (CL) is an essential phospholipid for the unique cristae structure of the mitochondrial inner membrane . Accumulating evidence suggests that mitochondrial dysfunction can result from the destruction of cristae structure due to CL remodeling. − CL, located exclusively in the inner membrane of mitochondria (IMM), is composed of two phosphate and four fatty acid moieties and plays a crucial role in maintaining proper protein complex function by inducing negative curvature and ensuring membrane structure stability . Pathological CL remodeling, induced by peroxidation and CL content reduction, leads to membrane leakage and a loss of function of IMM protein complexes.…”