PROANTHOCYANIDINS INHIBIT ERASTIN-INDUCED CELL FERROPTOSIS VIA NRF2

CUI Dan-dan, ZHANG Xiao-qiang

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (1) : 40-47.

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (1) : 40-47.
ORIGINAL ARTICLES

PROANTHOCYANIDINS INHIBIT ERASTIN-INDUCED CELL FERROPTOSIS VIA NRF2

  • CUI Dan-dan1,2, ZHANG Xiao-qiang1,2
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Abstract

Objective To investigate the effect of proanthocyanidins (PC) on erastin-induced ferroptosis in human neuroblastoma SH-SY5Y cells and the mechanism of action. Methods Cell viability was detected by thiazolyl blue tetrazolium bromide (MTT) colorimetric method. Intracellular iron ion level, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, glutathione (GSH) level and superoxide dismutase (SOD) activity were detected by corresponding kits. The protein expression levels of intracellular solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nfr2) and heme oxygenase 1 (HO-1) were measured by Western blot assay. Results PC pretreatment was able to protect SH-SY5Y cells from erastin-induced cellular ferroptosis, mainly by inhibiting ROS production, elevated iron ion levels and MDA production, upregulating GSH levels and SOD activity. In addition, PC could also upregulate the expressions of SLC7A11 and GPX4 by activating the Nrf2/HO-1 signaling pathway, while the Nrf2 inhibitor ML385 significantly abolished the inhibitory effect of PC on intracellular ferroptosis, and the protein expressions of SLC7A11, GPX4, Nrf2 and HO-1 were decreased. Conclusion PC can inhibit erastin-induced ferroptosis, thus exerting its neuroprotective effect, and the underlying mechanism may be related to the Nrf2/HO-1signaling pathway.

Key words

proanthocyanidins / ferroptosis / Nrf2/HO-1

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CUI Dan-dan, ZHANG Xiao-qiang. PROANTHOCYANIDINS INHIBIT ERASTIN-INDUCED CELL FERROPTOSIS VIA NRF2[J]. Acta Nutrimenta Sinica. 2024, 46(1): 40-47

References

[1] Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149:1060–1072.
[2] Morris G, Berk M, Carvalho AF, et al. Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases[J]. Behav Brain Res, 2018, 341:154–175.
[3] Hambright WS, Fonseca RS, Chen L, Na R, et al. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration[J]. Redox Biol, 2017, 12:8–17.
[4] Do Van B, Gouel F, Jonneaux A, et al. Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC[J]. Neurobiol Dis, 2016, 94:169–178.
[5] Chen L, Hambright WS, Na R, et al. Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis[J]. J Biol Chem, 2015, 290:28097–28106.
[6] Gao JM, Ma CJ, Xia DY, et al. Icariside II precondi- tioning evokes robust neuroprotection against ischaemic stroke, by targeting Nrf2 and the OXPHOS/NF-κB/ ferroptosis pathway[J]. Br J Pharmacol, 2023,180:308–329.
[7] Kenny EM, Fidan E, Yang Q, et al. Ferroptosis contributes to neuronal death and functional outcome after traumatic brain injury[J]. Crit Care Med, 2019, 47:410–418.
[8] Chinnery PF, Crompton DE, Birchall D, et al. Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation[J]. Brain, 2007, 130:110–119.
[9] Curtis ARJ, Fey C, Morris CM, et al. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease[J]. Nat Genet, 2001, 28:350–354.
[10] Sultana R, Perluigi M, Butterfield DA.Lipid peroxide- tion triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain[J]. Free Radic Biol Med, 2013, 62:157–169.
[11] Sies H, Jones DP.Reactive oxygen species (ROS) as pleiotropic physiological signalling agents[J]. Nat Rev Mol Cell Biol, 2020, 21:363–383.
[12] 程茂军, 郭杰, 刘婧, 等. Nrf2及天然产物导向的Nrf2激活剂研究进展[J]. 天然产物研究与开发, 2021, 33:165–177.
[13] Dodson M, Castro-Portuguez R, Zhang DD.NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis[J]. Redox Biol, 2019, 23:101107.
[14] Song X, Long D.Nrf2 and Ferroptosis: A new research direction for neurodegenerative diseases[J]. Front Neurosci, 2020, 14:267.
[15] Anandhan A, Chen W, Nguyen N, et al.α-Syn overexpression, NRF2 suppression, and enhanced ferroptosis create a vicious cycle of neuronal loss in Parkinson's disease[J]. Free Radic Biol Med, 2022, 192:130–140.
[16] Loboda A, Damulewicz M, Pyza E, et al. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism[J]. Cell Mol Life Sci, 2016, 73:3221–3247.
[17] Jiang T, Cheng H, Su J, et al. Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway[J]. Toxicol in Vitro, 2020, 62:104715.
[18] Huang Q, Ji D, Tian X, et al. Berberine inhibits erastin-induced ferroptosis of mouse hippocampal neuronal cells possibly by activating the Nrf2-HO-1/ GPX4 pathway[J]. Nan Fang Yi Ke Da Xue Xue Bao, 2022, 42:937–943.
[19] Ali T, Kim T, Rehman SU, et al. Natural dietary supplementation of anthocyanins via PI3K/Akt/Nrf2/HO-1 pathways mitigate oxidative stress, neurodegeneration, and memory impairment in a mouse model of Alzheimer’s disease[J]. Mol Neurobiol, 2018, 55:6076–6093.
[20] Wang Y, Gao L, Chen J, et al. Pharmacological modulation of Nrf2/HO-1 signaling pathway as a therapeutic target of Parkinson’s disease[J]. Front Pharmacol, 2021, 12:757161.
[21] Grau-Bove C, Sierra-Cruz M, Miguens-Gomez A, et al. A ten-day grape seed procyanidin treatment prevents certain ageing processes in female rats over the long term[J]. Nutrients, 2020, 12:3647.
[22] El-Shitany NA, Eid B.Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway[J]. Environ Toxicol, 2017, 32:1952–1963.
[23] Choi YH, Song CH, Mun SP.Proanthocyanidin-rich Pinus radiata bark extract inhibits mast cell-mediated anaphylaxis-like reactions[J]. Phytother Res, 2018, 32:290–297.
[24] Huang H, Yan P, Sun T, et al. Procyanidins extracted from lotus seedpod ameliorate amyloid-beta-induced toxicity in rat pheochromocytoma cells[J]. Oxid Med Cell Longev, 2018, 2018:4572893.
[25] Chen J, Chen Y, Zheng Y, et al. Protective effects and mechanisms of procyanidins on parkinson's disease in vivo and in vitro[J]. Molecules, 2021, 26:5558.
[26] Xuan M, Guan X, Gu Q, et al. Different iron deposition patterns in early- and middle-late-onset Parkinson's disease[J]. Parkinsonism Relat Disord, 2017, 44:23–27.
[27] Ayton S, Fazlollahi A, Bourgeat P, et al. Cerebral quantitative susceptibility mapping predicts amyloid- beta-related cognitive decline[J]. Brain, 2017, 140:2112–2119.
[28] Angelova PR, Horrocks MH, Klenerman D, et al. Lipid peroxidation is essential for α-synuclein-induced cell death[J]. J Neurochem, 2015, 133:582–589.
[29] Hirschhorn T, Stockwell BR.The development of the concept of ferroptosis[J]. Free Radic Biol Med, 2019, 133:130–143.
[30] Yang WS, Stockwell BR.Ferroptosis:Death by lipid peroxidation[J]. Trends Cell Biol, 2016, 26:165–176.
[31] Koppula P, Zhang Y, Zhuang L, et al. Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer[J]. Cancer Commun (Lond), 2018, 38:12.
[32] Proneth B, Conrad M.Ferroptosis and necroinflammation, a yet poorly explored link[J]. Cell Death Differ, 2019, 26:14–24.
[33] Liu T, Jiang L, Tavana O, et al. The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SLC7A11[J]. Cancer Res, 2019, 79:1913–1924.
[34] Ursini F, Maiorino M, Gregolin C.The selenoenzyme phospholipid hydroperoxide glutathione peroxidase[J]. Biochim Biophys Acta, 1985, 839:62–70.
[35] Abdalkader M, Lampinen R, Kanninen KM, et al. Targeting Nrf2 to suppress ferroptosis and mito-chondrial dysfunction in neurodegeneration[J]. Front Neurosci, 2018, 12:466.
[36] Ma H, Wang X, Zhang W, et al. Melatonin suppresses ferroptosis induced by high glucose via activation of the Nrf2/HO-1 signaling pathway in type 2 diabetic osteoporosis[J]. Oxid Med Cell Longev, 2020, 2020:9067610.
[37] Yuan Y, Zhai Y, Chen J, et al. Kaempferol ameliorates oxygen-glucose deprivation/reoxygenation-induced ne-uronal ferroptosis by activating Nrf2/SLC7A11/ GPX4 Axis[J]. Biomolecules, 2021, 11:923.

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