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Objective To investigate the effects of zeaxanthin (Zea) on apoptosis, oxidative stress, mitochondrial dysfunction and Akt/GSK3β pathway of SH-SY5Y cells induced by tunicamycin (TM). Methods The cells were divided into 4 groups: The control, TM-induced injury (5 μg/mL TM), Zea (5 μmol/L Zea) and injury plus protection group (5 μmol/L Zea pretreatment+5 μg/mL TM co-treatment). The intracellular reactive oxygen species level was detected by flow cytometry. Mitochondrial dysfunction was analyzed by Seahorse XF cell energy metabolism instrument. The expressions of apoptosis-related proteins Bcl-2 and Bax, oxidative stress-related proteins Nrf2, Akt, p-Akt, GSK3β and p-GSK3β were determined by Western Blot. Results Zea (5 μmol/L) exerted a protective effect against apoptosis, increased the expression of the anti-apoptotic protein Bcl-2 and decreased the pro-apoptotic protein Bax/Bcl-2 ratio; alleviated cellular oxidative stress, decreased TM-induced intracellular reactive oxygen species levels, and up-regulated the expression of the antioxidant protein nuclear factor E2-related factor (Nrf2); and increased the rate of oxygen consumption of the damaged cells, enhanced proton leakage capacity and spare respiratory capacity. Endoplasmic reticulum stress (ERS) decreased Akt activity, while down-regulating the phosphorylation level of its Ser473 site, which in turn weakened the phosphorylation level of the downstream GSK3β Ser9 site, leading to an increase in GSK3β activity, and Zea exerted a mitigating effect on TM-induced changes in this pathway. Conclusion Zea significantly alleviated TM-induced endoplasmic reticulum stress injury through multiple mechanisms, with potential applications in the prevention and treatment of Alzheimer’s disease in the early pathological process.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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