Phytochemicals prevent mitochondrial membrane permeabilization and protect SH-SY5Y cells against apoptosis induced by PK11195, a ligand for outer membrane translocator protein
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- 作者：Yuqiu Wu ; Masayo Shamoto-Nagai ; Wakako Maruyama…
- 关键词：Phytochemicals ; Neuroprotection ; Apoptosis ; Superoxide flash ; Calcium ; PK11195
- 刊名：Journal of Neural Transmission
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：124
- 期：1
- 页码：89-98
- 全文大小：
- 刊物类别：Medicine
- 刊物主题：Neurology; Psychiatry; Pharmacology/Toxicology; Neurosciences;
- 出版者：Springer Vienna
- ISSN：1435-1463
- 卷排序：124
文摘
Epidemiological studies present the beneficial effects of dietary habits on prevention of aging-associated decline of brain function. Phytochemicals, the second metabolites of food, protect neuronal cells from cell death in cellular models of neurodegenerative disorders, and the neuroprotective activity has been ascribed to the anti-oxidant and anti-inflammatory functions. In this paper, the cellular mechanism of neuroprotection by phytochemicals was investigated, using the cellular model of mitochondrial apoptosis induced by PK11195, a ligand of outer membrane translocator protein, in SH-SY5Y cells. PK11195 induced mitochondrial membrane permeabilization with rapid transit production of superoxide (superoxide flashes) and calcium release from mitochondria, and activated apoptosis signal pathway. Study on the structure–activity relationship of astaxanthin, ferulic acid derivatives, and sesame lignans revealed that these phytochemicals inhibited mitochondrial membrane permeabilization and protected cells from apoptosis. Ferulic acid derivatives and sesame lignans inhibited or enhanced the mitochondrial pore formation and cell death by PK11195 according to their amphiphilic properties, not directly depending on the antioxidant activity. Regulation of pore formation at mitochondrial membrane is discussed as a novel mechanism behind neuroprotective activity of phytochemicals in aging and age-associated neurodegenerative disorders, and also behind dual functions of phytochemicals in neuronal and cancer cells.