title: Rotundarpene attenuates cholesterol oxidation product-induced apoptosis by suppressing the mitochondrial pathway and the caspase-8- and bid-dependent pathways.
abstract: The extract of from the barks of Ilex Rotunda Thunb has demonstrated anti-inflammatory and anti-oxidant effects. Nevertheless, the effect of rotundarpene (4-caffeoyl-3-methyl-but-2-ene-1,4-diol) on the neuronal cell death induced by cholesterol oxidation products is unclear. We assessed the preventive effect of rotundarpene on the cholesterol oxidation product-induced apoptosis in neuronal cells using differentiated PC12 cells. 7-Ketocholesterol and 25-hydroxycholesterol induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels, increase in Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), cleavage of PARP-1 and an increase in the tumor suppressor p53 levels. Rotundarpene attenuated the cholesterol oxidation product-induced changes in the apoptosis-related protein levels, formation of reactive oxygen species, depletion of GSH, nuclear damage and cell death. The results show that rotundarpene may attenuate the cholesterol oxidation product-induced apoptosis in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect appears to be attributed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH. Rotundarpene appears to attenuate cholesterol-oxidation product-mediated neuronal degeneration.
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Da Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, SoonChunHyang University Hospital, Bucheon City, Kyung-Gi-Do 420-767, South Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chung-Ang University Hospital, Seoul 156-755, South Korea.
authors.forename: Dong Suep
authors.initials: DS
authors.lastname: Sohn
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: leecs@cau.ac.kr.
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D045782:Hemiterpenes / Q000494:pharmacology*; D007653:Ketocholesterols; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D016716:PC12 Cells; D051381:Rats
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494816:Bid protein, rat; D002109:Caffeic Acids; D045782:Hemiterpenes; D007653:Ketocholesterols; C000591680:rotundarpene; D045304:Cytochromes c; D002784:Cholesterol; C505528:Casp8 protein, rat; D053181:Caspase 8; D005978:Glutathione; C003001:7-ketocholesterol
keywords: Apoptosis-related proteins; Cholesterol oxidation product; PC12 cells; Protection; Rotundarpene