Palmitic acid triggers cell apoptosis in RGC-5 retinal ganglion cells through the Akt/FoxO1 signaling pathway
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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RGCs are known to be sensitive to lipotoxicity.
“aligning with the known sensitivity of RGCs to lipotoxicity19.”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [19]
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Neurotoxic reactive astrocytes induce cell death via saturated lipids
Guttenplan, K. A., Weigel, M. K., Prakash, P., Wijewardhane, P. R., Hasel, P., Rufen-Blanchette, U., Münch, A. E., Blum, J. A., Fine, J., Neal, M. C., et al. (2021) · Nature · doi:10.1038/s41586-021-03960-y · Cited by 578 · see citing works
- Authors
- Yan, P., Tang, S., Zhang, H., Guo, Y., Zeng, Z., & Wen, Q.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Zhengzhou University (CN)
- Corresponding author
- Zeng, Zhiwen
- Wen, Qiang
- Venue
- Metabolic Brain Disease
- Published
- 2016-12-07
- Volume
- 32
- Issue
- 2
- Pages
- 453-460
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- OpenAlex
- W2559968880
- Cited by
- 17
- References
- 35
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 2
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Zhengzhou University
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- palmitic acid, lipotoxicity, retinal ganglion cells, apoptosis, glaucoma, PI3K/Akt signaling, oxidative stress, reactive oxygen species, malondialdehyde, RGC-5 cells
- MeSH terms
- Forkhead Box Protein O1, Animals, Cell Line, Malondialdehyde, Nerve Tissue Proteins, Retinal Ganglion Cells, Tetrazolium Salts, Thiazoles, Signal Transduction, Apoptosis, Reactive Oxygen Species, Palmitic Acid, RNA, Small Interfering, Oncogene Protein v-akt, Rats, Gene Knockdown Techniques
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