Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury
2021
Authors:
Todorović, ZoranĐurašević, Siniša
Stojković, Maja
Grigorov, Ilijana
Pavlović, Slađan
Jasnić, Nebojša
Tosti, Tomislav
Bjekić Macut, Jelica
Thiemermann, Christoph
Đorđević, Jelena
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.
Keywords:
Ischemia/reperfusion; Kidney; Lipidomics; LiverSource:
International Journal of Molecular Sciences, 2021, 22, 6, 2798-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200110 (University of Belgrade, Faculty of Medicine) (RS-MESTD-inst-2020-200110)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- COST Action CA19105