title: 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.
authors.affiliation: Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
authors.forename: Panshi
authors.initials: P
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shenzhen Mental Health Center and Shenzhen Key Lab for Psychological Healthcare, Shenzhen, 518020, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Shenzhen Mental Health Center and Shenzhen Key Lab for Psychological Healthcare, Shenzhen, 518020, People's Republic of China. zengzw1122@163.com.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Clinical Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China. qiangwen7619@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D055785:Gene Knockdown Techniques; D008315:Malondialdehyde / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000187:drug effects*; D019308:Palmitic Acid / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D000071161:Forkhead Box Protein O1
chemical_list: D008315:Malondialdehyde; D009419:Nerve Tissue Proteins; D051058:Oncogene Protein v-akt; D019308:Palmitic Acid; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C022616:thiazolyl blue
keywords: Akt/FoxO1; Apoptosis; Palmitic acid; RGC-5; Retinal ganglion cells