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Neuroprotective Effects of n-3 Polyunsaturated Fatty Acid-Enriched Phosphatidylserine Against Oxidative Damage in PC12 Cells

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Abstract

Neurodegenerative diseases are defined by progressive loss of specific neuronal cell populations and are associated with protein aggregates. Oxidative stress has been implicated in their pathological processes. Previous studies revealed that docosahexaenoic acid (DHA) is beneficial in neurodegenerative diseases. Phospholipids (PLs) derived from marine products are rich in DHA and eicosapentaenoic acid (EPA). In the present study, we investigated the neuroprotective effects of DHA-enriched and unenriched phosphatidylcholine (PC) and phosphatidylserine (PS) on oxidative stress induced by hydrogen peroxide (H2O2) and tert-butylhydroperoxide in PC12 cells. Cell viability and leakage of lactate dehydrogenase results showed that the neuroprotective effect of PS was superior to that of PC. DHA- and EPA-enriched PC and PS were superior to that without DHA or EPA; in addition, the improvement with n-3 polyunsaturated fatty acid-enriched PS (n-3 PS) was dose dependent. Acridine orange/ethidium bromide staining showed that DHA- and EPA-enriched PS (DHA/EPA-PS) could significantly inhibit apoptosis. Mechanistic studies revealed that EPA-PS and DHA-PS were effective to increase superoxide dismutase (SOD) levels by 48.4 and 58.2 % and total antioxidant capacity (T-AOC) level by 51 and 94 %, respectively, in the H2O2 model. Similar results for SOD and T-AOC levels were shown in the t-BHP model. EPA/DHA-PS could downregulate the messenger RNA level of Caspase-3, Caspase-9, and Bax, upregulate Bcl-2, inhibit Bax, and increase Bcl-2 at protein level. In conclusion, EPA/DHA-PS could protect PC12 cells from oxidative stress and prevent mitochondrial-mediated apoptosis. Our findings indicate that the neuroprotective effects of DHA/EPA-PLs depend on the molecular form. Further studies are necessary to reveal detailed mechanisms and structure–effect relationships.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 31371757) and the project supported by the State Key Program of National Natural Science of China (No. 31330060).

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  1. Hongxia Che and Xueyuan Fu contributed equally to this work.

Authors and Affiliations

  1. College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China

    Hongxia Che, Lingyu Zhang, Xiang Gao, Min Wen, Changhu Xue, Jie Xu & Yuming Wang

  2. Marine Biomedical Research Institute of Qingdao, No. 23 Hong Kong East Road, Qingdao, Shandong, China

    Xueyuan Fu

  3. Division of Marine Life Science, Faculty of Fisheries Sciences, Hokkaido University, Hakodate, 041-8611, Japan

    Lei Du

  4. Department of Nutrition and Food Hygiene, School of Public Health, Shandong University, 44 Wenhua Xilu, Jinan, 250012, China

    Lei Du

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  1. Hongxia Che
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  2. Xueyuan Fu
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Correspondence to Jie Xu or Yuming Wang.

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Che, H., Fu, X., Zhang, L. et al. Neuroprotective Effects of n-3 Polyunsaturated Fatty Acid-Enriched Phosphatidylserine Against Oxidative Damage in PC12 Cells. Cell Mol Neurobiol 38, 657–668 (2018). https://doi.org/10.1007/s10571-017-0516-y

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