title: The anti-apoptotic action of 5-hydroxyindole: protection of mitochondrial integrity.
abstract: 5-Hydroxyindole (5HI), a metabolite of tryptophan, is involved in learning and memory, central neuron system regulation, and anti-oxidant activity. However, its protective action in mitochondrial function is not clear. Here, we tested whether 5HI protects against tert-butylhydroperoxide (t-BHP)-induced oxidative damage and mitochondrial dysfunction in human fibroblast cells. 5HI significantly suppressed t-BHP-induced cytotoxicity as determined by intracellular reactive species generation, lipid peroxidation, glutathione depletion, and peroxynitrite (ONOO(-)) generation. In addition, 5HI reduced t-BHP-induced DNA condensation. Pretreatment with 5HI significantly restored mitochondrial membrane potential (Deltapsim), suggesting that it protected cells against t-BHP-induced apoptosis. Western blot analysis also revealed that 5HI markedly inhibited cytochrome c release and caspase-3 activation, but not caspase-9 activation. Our data suggest that 5HI protects cells by attenuating oxidative stress and consequently protects against mitochondrial dysfunction.
authors.affiliation: Department of Pharmacy, Pusan National University, Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Bae
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Jehun
authors.initials: J
authors.lastname: Choi
authors.forename: Hyoung-Sam
authors.initials: HS
authors.lastname: Heo
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000009:adverse effects
chemical_list: D007211:Indoles; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; C026785:5-hydroxyindole; D045304:Cytochromes c; D020122:tert-Butylhydroperoxide; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione