Dihydrolipoic acid prevents hypoxic/reoxygenation and peroxidative damage in rat heart mitochondria.
Fluorescence anisotropy (r) was determined in hypoxic/reoxygenating rat heart mitochondria by means of 1,6-diphenyl-1,3,5-hexatriene. During hypoxia, values for r increased, indicating a rigidified membrane. Membrane fluidity was increased when 20 pmol to 2 nmol/mg protein of dihydrolipoic acid (DHL) was present during hypoxia. Dithiothreitol (DTT) or 2-mercaptopropionylglycin (MPG) at similar concentration did not result in membrane fluidization under these conditions. Peroxidative damage was induced in mitochondria by H2O2. In the presence of 2 nmol/mg protein of DHL, malondialdehyde production was decreased by 50%. DTT or MPG brought about only a 25% decrease. These results were corroborated by spin label studies with 4-maleimido-TEMPO and 5-proxylnonane (5-P-9); H2O2 induced a decrease in fluidity in the region of labeled thiol groups and an increase in polarity sensed by 5-P-9. DHL proved efficient in reducing such fluidity and polarity changes.
Scheer
B
B
Gustav-Embden-Zentrum der Biologischen Chemie, Universität Frankfurt, Germany.
Zimmer
G
G
D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004161:Diphenylhexatriene; D004220:Disulfides / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005454:Fluorescence Polarization; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D007425:Intracellular Membranes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects*; D010100:Oxygen / Q000009:adverse effects*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013113:Spin Labels; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008625:Tiopronin / Q000494:pharmacology
D003497:Cyclic N-Oxides; D004220:Disulfides; D011759:Pyrrolidines; D013113:Spin Labels; C081054:5-proxylnonane; D004161:Diphenylhexatriene; D008315:Malondialdehyde; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D006861:Hydrogen Peroxide; D008625:Tiopronin; D010100:Oxygen; D004229:Dithiothreitol