Piperine inhibition of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells.
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.
Lee
Chung Soo
CS
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
Han
Eun Sook
ES
Kim
Young Ki
YK
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
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