The anti-apoptotic action of 5-hydroxyindole: protection of mitochondrial integrity.
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.
Bae
Sung Jin
SJ
Department of Pharmacy, Pusan National University, Korea.
Lee
Jun Sik
JS
Lee
Eun Kyeong
EK
Kim
Ji Min
JM
Choi
Jehun
J
Heo
Hyoung-Sam
HS
Yu
Byung Pal
BP
Chung
Hae Young
HY
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
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