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Palmitic acid triggers cell apoptosis in RGC-5 retinal ganglion cells through the Akt/FoxO1 signaling pathway

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Abstract

Hallmarks of the pathophysiology of glaucoma are oxidative stress and apoptotic death of retinal ganglion cells (RGCs). Lipotoxicity, involving a series of pathological cellular responses after exposure to elevated levels of fatty acids, leads to oxidative stress and cell death in various cell types. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O1 (PI3K/Akt/FoxO1) pathway is crucial for cell survival and apoptosis. More importantly, FoxO1 gene has been reported to confer relatively higher risks for eye diseases including glaucoma. However, little information is available regarding the interaction between FoxO1 and RGC apoptosis, much less a precise mechanism. In the present study, immortalized rat retinal ganglion cell line 5 (RGC-5) was used as a model to study the toxicity of palmitic acid (PA), as well as underlying mechanisms. We found that PA exposure significantly decreased cell viability by enhancing apoptosis in RGC-5 cells, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. PA also induced a remarkable increase in reactive oxygen species and malondialdehyde. Moreover, PA significantly decreased the level of phospho-Akt and phospho-FoxO1 in cells. Finally, shRNA knockdown and plasmid overexpression studies displayed that downregulation of Akt protein or upregulation of FoxO1 protein augmented cell death, while knockdown of FoxO1 or overexpression of Akt1 abolished PA-induced cell death. Collectively, our results indicated that PA-induced cell death is mediated through modulation of Akt/FoxO1 pathway activity.

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Acknowledgements

This work was supported by funding from the National Natural Science Fund of China (No U1304815) and Outstanding Young Talent Research Fund of Zhengzhou University.

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Authors and Affiliations

  1. Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China

    Panshi Yan

  2. Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China

    Shu Tang

  3. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China

    Haifeng Zhang

  4. Shenzhen Mental Health Center and Shenzhen Key Lab for Psychological Healthcare, Shenzhen, 518020, People’s Republic of China

    Yuanyuan Guo & Zhiwen Zeng

  5. Department of Clinical Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China

    Qiang Wen

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  1. Panshi Yan
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  2. Shu Tang
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  3. Haifeng Zhang
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Correspondence to Zhiwen Zeng or Qiang Wen.

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Panshi Yan and Shu Tang contributed equally to this work.

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Yan, P., Tang, S., Zhang, H. et al. Palmitic acid triggers cell apoptosis in RGC-5 retinal ganglion cells through the Akt/FoxO1 signaling pathway. Metab Brain Dis 32, 453–460 (2017). https://doi.org/10.1007/s11011-016-9935-6

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  • DOI: https://doi.org/10.1007/s11011-016-9935-6

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