Glycyrrhizin prevents 7-ketocholesterol toxicity against differentiated PC12 cells by suppressing mitochondrial membrane permeability change.
Defects in mitochondrial function participate in the induction of neuronal cell injury. In neurodegenerative conditions, oxidative products of cholesterol are elevated and oxysterols seem to be implicated in neuronal cell death. The present work was designed to study the inhibitory effect of licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid against the toxicity of 7-ketocholesterol in relation to the mitochondria-mediated cell death process. 7-Ketocholesterol induced the nuclear damage, loss of the mitochondrial transmembrane potential, increase in the cytosolic Bax and cytochrome c levels, caspase-3 activation and cell death in differentiated PC12 cells. Glycyrrhizin and 18beta-glycyrrhetinic acid prevented the 7-ketocholesterol-induced mitochondrial damage, leading to caspase-3 activation and cell death. The results obtained show that glycyrrhizin and 18beta-glycyrrhetinic acid may prevent the 7-ketocholesterol-induced neuronal cell damage by suppressing changes in the mitochondrial membrane permeability.
Kim
Doo Eung
DE
Department of Neurology, Seoul Veterans Hospital, Seoul 134-791, South Korea.
Youn
Young Chul
YC
Kim
Young Ki
YK
Hong
Ki Moo
KM
Lee
Chung Soo
CS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D007653:Ketocholesterols / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects*; D016716:PC12 Cells; D010539:Permeability / Q000187:drug effects; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007653:Ketocholesterols; D051028:bcl-2-Associated X Protein; C119129:18alpha-glycyrrhetinic acid; D019695:Glycyrrhizic Acid; D045304:Cytochromes c; D053148:Caspase 3; C003001:7-ketocholesterol; D006034:Glycyrrhetinic Acid