Effects of epigallocatechin‑3‑gallate on iron metabolism in spinal cord motor neurons

Che,Fengyuan; Wang,Guangying; Yu,Jixu; Wang,Xianjun; Lu,Yucheng; Fu,Qingxi; Su,Quanping; Jiang,Jianzhang; Du,Yifeng

doi:10.3892/mmr.2017.6919

Effects of epigallocatechin‑3‑gallate on iron metabolism in spinal cord motor neurons

Authors:
- Fengyuan Che
- Guangying Wang
- Jixu Yu
- Xianjun Wang
- Yucheng Lu
- Qingxi Fu
- Quanping Su
- Jianzhang Jiang
- Yifeng Du
View Affiliations

Affiliations: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China, Central Laboratory, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
Published online on: July 5, 2017 https://doi.org/10.3892/mmr.2017.6919
Pages: 3010-3014

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Accumulating evidence suggests that iron homeostasis is disordered in amyotrophic lateral sclerosis (ALS). In view of the promising performance of epigallocatechin‑3‑gallate (EGCG) in neuroprotection studies, the present study aimed to verify whether EGCG protects motor neurons in an ALS model, and whether it has any effects on iron metabolism using an ELISA and western blotting. The results demonstrated that EGCG decreased oxidative stress and protected motor neurons in the organotypic culture of the rat spinal cord. Furthermore, total iron levels increased significantly in the spinal cord following 3 weeks of treatment with threo‑hydroxyaspartate. In addition, the expression of influx proteins (transferrin receptor and divalent metal‑ion transporter 1) increased significantly. However, EGCG demonstrated no effect on total iron levels and the expression of influx proteins. In conclusion, EGCG leads to a decrease in oxidative stress levels, leading to motor neuron protection in the organotypic culture of a rat spinal cord; however, EGCG does not alter iron metabolism protein expression regulation.

View Figures

View References

1	Zarei S, Carr K, Reiley L, Diaz K, Guerra O, Altamirano PF, Pagani W, Lodin D, Orozco G and Chinea A: A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 6:1712015. View Article : Google Scholar : PubMed/NCBI
2	Jeong SY, Rathore KI, Schulz K, Ponka P, Arosio P and David S: Dysregulation of iron homeostasis in the CNS contributes to disease progression in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 29:610–619. 2009. View Article : Google Scholar : PubMed/NCBI
3	Hadzhieva M, Kirches E, Wilisch-Neumann A, Pachow D, Wallesch M, Schoenfeld P, Paege I, Vielhaber S, Petri S, Keilhoff G and Mawrin C: Dysregulation of iron protein expression in the G93A model of amyotrophic lateral sclerosis. Neuroscience. 230:94–101. 2013. View Article : Google Scholar : PubMed/NCBI
4	Hozumi I, Hasegawa T, Honda A, Ozawa K, Hayashi Y, Hashimoto K, Yamada M, Koumura A, Sakurai T, Kimura A, et al: Patterns of levels of biological metals in CSF differ among neurodegenerative diseases. J Neurol Sci. 303:95–99. 2011. View Article : Google Scholar : PubMed/NCBI
5	Su XW, Clardy SL, Stephens HE, Simmons Z and Connor JR: Serum ferritin is elevated in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 16:102–107. 2015. View Article : Google Scholar : PubMed/NCBI
6	Langkammer C, Enzinger C, Quasthoff S, Grafenauer P, Soellinger M, Fazekas F and Ropele S: Mapping of iron deposition in conjunction with assessment of nerve fiber tract integrity in amyotrophic lateral sclerosis. J Magn Reson Imaging. 31:1339–1345. 2010. View Article : Google Scholar : PubMed/NCBI
7	Yu J, Qi F, Wang N, Gao P, Dai S, Lu Y, Su Q, Du Y and Che F: Increased iron level in motor cortex of amyotrophic lateral sclerosis patients: An in vivo MR study. Amyotroph Lateral Scler Frontotemporal Degener. 15:357–361. 2014. View Article : Google Scholar : PubMed/NCBI
8	Kwan JY, Jeong SY, Van Gelderen P, Deng HX, Quezado MM, Danielian LE, Butman JA, Chen L, Bayat E and Russell J: Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: Correlating 7 tesla MRI and pathology. PLoS One. 7:e352412012. View Article : Google Scholar : PubMed/NCBI
9	Reznichenko L, Amit T, Zheng H, Avramovich-Tirosh Y, Youdim MB, Weinreb O and Mandel S: Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (−)-epigallocatechin-3-gallate in cell cultures: Implications for iron chelation in Alzheimer's disease. J Neurochem. 97:527–536. 2006. View Article : Google Scholar : PubMed/NCBI
10	Weinreb O, Amit T and Youdim MB: The application of proteomics for studying the neurorescue activity of the polyphenol (−)-epigallocatechin-3-gallate. Arch Biochem Biophys. 476:152–160. 2008. View Article : Google Scholar : PubMed/NCBI
11	Mandel S, Weinreb O, Amit T and Youdim MB: Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (−)-epigallocatechin-3-gallate: Implications for neurodegenerative diseases. J Neurochem. 88:1555–1569. 2004. View Article : Google Scholar : PubMed/NCBI
12	Koh SH, Lee SM, Kim HY, Lee KY, Lee YJ, Kim HT, Kim J, Kim MH, Hwang MS, Song C, et al: The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett. 395:103–107. 2006. View Article : Google Scholar : PubMed/NCBI
13	Xu Z, Chen S, Li X, Luo G, Li L and Le W: Neuroprotective effects of (−)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res. 31:1263–1269. 2006. View Article : Google Scholar : PubMed/NCBI
14	Rothstein JD, Jin L, Dykes-Hoberg M and Kuncl RW: Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity. Proc Natl Acad Sci USA. 90:6591–6595. 1993. View Article : Google Scholar : PubMed/NCBI
15	Yu J, Guo Y, Sun M, Li B, Zhang Y and Li C: Iron is a potential key mediator of glutamate excitotoxicity in spinal cord motor neurons. Brain Res. 27:102–107. 2009. View Article : Google Scholar
16	Yu J, Jia Y, Guo Y, Chang G, Duan W, Sun M, Li B and Li C: Epigallocatechin-3-gallate protects motor neurons and regulates glutamate level. FEBS Lett. 584:2921–2925. 2010. View Article : Google Scholar : PubMed/NCBI
17	Jomova K, Vondrakova D, Lawson M and Valko M: Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 345:91–104. 2010. View Article : Google Scholar : PubMed/NCBI
18	Petri S, Korner S and Kiaei M: Nrf2/ARE signaling pathway: Key mediator in oxidative stress and potential therapeutic target in ALS. Neurol Res Int. 2012:8780302012.PubMed/NCBI
19	Hadzhieva M, Kirches E and Mawrin C: Review: Iron metabolism and the role of iron in neurodegenerative disorders. Neuropathol Appl Neurobiol. 40:240–257. 2014. View Article : Google Scholar : PubMed/NCBI
20	Ward RJ, Dexter DT and Crichton RR: Neurodegenerative diseases and therapeutic strategies using iron chelators. J Trace Elem Med Biol. 31:267–273. 2015. View Article : Google Scholar : PubMed/NCBI
21	Silani V, Braga M, Ciammola A, Cardin V and Scarlato G: Motor neurones in culture as a model to study ALS. J Neurol. 247:(Suppl 1). SI28–SI36. 2000. View Article : Google Scholar
22	Carriedo SG, Sensi SL, Yin HZ and Weiss JH: AMPA exposures induce mitochondrial Ca(2+) overload and ROS generation in spinal motor neurons in vitro. J Neurosci. 20:240–250. 2000.PubMed/NCBI
23	Mandel S and Youdim MB: Catechin polyphenols: Neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med. 37:304–317. 2004. View Article : Google Scholar : PubMed/NCBI
24	Weinreb O, Amit T, Mandel S and Youdim MB: Neuroprotective molecular mechanisms of (−)-epigallocatechin-3-gallate: A reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes Nutr. 4:283–296. 2009. View Article : Google Scholar : PubMed/NCBI
25	Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T and Youdim MB: Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals. 14:46–60. 2005. View Article : Google Scholar : PubMed/NCBI
26	Mandel SA, Amit T, Kalfon L, Reznichenko L, Weinreb O and Youdim MB: Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: Special reference to epigallocatechin gallate (EGCG). J Alzheimers Dis. 15:211–222. 2008. View Article : Google Scholar : PubMed/NCBI