title: Piperine inhibition of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells.
abstract: The effect of alkaloid piperine against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in differentiated PC12 cells was assessed. Piperine treatment revealed a differential effect on the cytotoxicity of MPP(+) and had its maximum inhibitory effect at 1 microM. The addition of piperine (0.5-10 microM) significantly reduced the MPP(+)-induced nuclear damage, mitochondrial membrane permeability changes, formation of reactive oxygen species and depletion of GSH. In contrast, piperine at 50-100 microM showed cytotoxicity and exhibited an additive effect against the MPP(+) toxicity. The results indicate that piperine had a differential effect on the cytotoxicity of MPP(+) depending on concentration. Piperine at low concentrations may reduce the MPP(+)-induced viability loss in PC12 cells by suppressing the changes in the mitochondrial membrane permeability, leading to the release of cytochrome c and subsequent activation of caspase-3. The effects may be ascribed to its inhibitory action on the formation of reactive oxygen species and depletion of GSH.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Han
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D052117:Benzodioxoles; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D045304:Cytochromes c / Q000096:biosynthesis; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D015655:1-Methyl-4-phenylpyridinium; C008922:piperine