Effect of folic acid on Parkinson's like injury of HT22 cells through the NLRP3/ASC/Caspase-1 signaling pathway

doi:10.3877/cma.j.issn.2095-9141.2022.04.002

Abstract

Abstract:

Objective

To investigate the effect of folic acid on Parkinson's like injury in mouse HT22 cells.

Methods

Mouse HT22 cells were used as the study subjects, and were randomly divided into four groups: Control group, MPP⁺ group (Model group), Folic acid group and MPP⁺ + Folic acid (Treatment group). CCK-8, LDH, TUNEL and immunofluorescence assay were used to detect the effect of folic acid on cell viability and expression of NLRP3 induced by MPP⁺. The effects of folic acid on the expression of NLRP3, ASC and Caspase-1 after MPP⁺-induced cell injury were detected by Western blot and qPCR. ELISA was used to detect the effect of folic acid on the expression of interleukin (IL)-18 and IL-1β after MPP⁺-induced cell injury. Finally, Western blot was used to examine the expression of ASC, Caspase-1, IL-18 and IL-1β after CY-09 treatment.

Results

MPP⁺ can cause Parkinson’s like injury to HT22 cells. The results of CCK-8, LDH and TUNEL experiments showed folic acid can significantly alleviate the decrease of cell viability and the increase of apoptotic cells caused by injury. Immunofluorescence test showed that folic acid could reduce the increase of NLRP3 fluorescence intensity in injured cells. Western blot and qPCR test showed that folic acid decreased the increase of NLRP3, ASC and Caspase-1 in protein level and mRNA level. ELISA results showed that folic acid treatment significantly alleviated the secretion of intracellular IL-18 and IL-1β after injury. Finally, Western blot showed that CY-09 could block the increase of ASC, Caspase-1 and IL-18 and IL-1β protein levels in cells after injury.

Conclusion

Folic acid can cause Parkinson's like injury to HT22 cells by decreasing IL-18 and IL-1β expression and protecting MPP⁺, and the potential protective mechanism may be closely related to the NLRP3/ASC/Caspase-1 signaling pathway.

Key words: Parkinson’s disease, Folic acid, NOD-like receptor protein 3, Interleukin-1β, Interleukin-18

Liya Ji, Ang Ji, Zhengli Di, Jing Xiong, Zhiqin Liu, Xiuyun Xue, Xiaowei Fei, Yanan Dou, Li Wang. Effect of folic acid on Parkinson's like injury of HT22 cells through the NLRP3/ASC/Caspase-1 signaling pathway[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2022, 08(04): 196-203.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsjcswkdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-9141.2022.04.002

https://zhsjcswkdzzz.cma-cmc.com.cn/EN/Y2022/V08/I04/196

Figures/Tables 6

References 24

[1]	Joshi N, Singh S. Updates on immunity and inflammation in Parkinson disease pathology[J]. J Neurosci Res, 2018, 96(3): 379-390.
[2]	Han X, Sun S, Sun Y, et al. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease[J]. Autophagy, 2019, 15(11): 1860-1881.
[3]	袁亮,陈立华.脑深部电刺激在新领域的临床应用进展[J].中华神经创伤外科电子杂志, 2016, 2(4): 235-240.
[4]	Ahmed S, Kwatra M, Ranjan Panda S, et al. Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease[J]. Brain Behav Immun, 2021, 91: 142-158.
[5]	Boelens Keun JT, Arnoldussen IA, Vriend C, et al. Dietary approaches to improve efficacy and control side effects of levodopa therapy in Parkinson's disease: a systematic review[J]. Adv Nutr, 2021, 12(6): 2265-2287.
[6]	Lei XW, Li Q, Zhang JZ, et al. The protective roles of folic acid in preventing diabetic retinopathy are potentially associated with suppressions on angiogenesis, inflammation, and oxidative stress[J]. Ophthalmic Res, 2019, 62(2): 80-92.
[7]	Mi S, Tang Y, Dari G, et al. Transcriptome sequencing analysis for the identification of stable lncRNAs associated with bovine staphylococcus aureus mastitis[J]. J Anim Sci Biotechnol, 2021, 12(1): 120.
[8]	Field MS, Stover PJ. Safety of folic acid[J]. Ann N Y Acad Sci, 2018, 1414(1): 59-71.
[9]	Liao X, Jiang Y, Dai Q, et al. Fluorofenidone attenuates renal fibrosis by inhibiting the mtROS-NLRP3 pathway in a murine model of folic acid nephropathy[J]. Biochem Biophys Res Commun, 2021, 534: 694-701.
[10]	Elsayed MS, Abu-Elsaad NM, Nader MA. The NLRP3 inhibitor dapansutrile attenuates folic acid induced nephrotoxicity via inhibiting inflammasome/caspase-1/IL axis and regulating autophagy/proliferation[J]. Life Sci, 2021, 285: 119974.
[11]	Srivastav S, Singh SK, Yadav AK, et al. Folic acid supplementation rescues anomalies associated with knockdown of parkin in dopaminergic and serotonergic neurons in drosophila model of Parkinson's disease[J]. Biochem Biophys Res Commun, 2015, 460(3): 780-785.
[12]	Srivastav S, Singh S, Yadav A, et al. Folic acid supplementation ameliorates oxidative stress, metabolic functions and developmental anomalies in a novel fly model of Parkinson's disease[J]. Neurochem Res, 2015, 40(7): 1350-1359.
[13]	陆宸宇,杨君,刘怡希,等.帕金森氏病关联miRNAs的功能和调控[J].中国临床药理学与治疗学, 2020, 25(7): 775-783.
[14]	Scherbaum R, Hartelt E, Kinkel M, et al. Parkinson's disease multimodal complex treatment improves motor symptoms, depression and quality of life[J]. J Neurol, 2020, 267(4): 954-965.
[15]	Haque ME, Akther M, Jakaria M, et al. Targeting the microglial NLRP3 inflammasome and its role in Parkinson's disease[J]. Mov Disord, 2020, 35(1): 20-33.
[16]	Broz P. Immunology: caspase target drives pyroptosis[J]. Nature, 2015, 526(7575): 642-643.
[17]	Tufekci KU, Ercan I, Isci KB, et al. Sulforaphane inhibits NLRP3 inflammasome activation in microglia through Nrf2-mediated miRNA alteration[J]. Immunol Lett, 2021, 233: 20-30.
[18]	Rui W, Li S, Xiao H, et al. Baicalein attenuates neuroinflammation by inhibiting NLRP3/caspase-1/GSDMD pathway in MPTP induced mice model of Parkinson's disease[J]. Int J Neuropsychopharmacol, 2020, 23(11): 762-773.
[19]	Yun SP, Kam TI, Panicker N, et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease[J]. Nat Med, 2018, 24(7): 931-938.
[20]	中国医药教育协会临床合理用药专业委员会,中国医疗保健国际交流促进会高血压分会,中国妇幼保健协会围产营养与代谢专业委员会,等.中国临床合理补充叶酸多学科专家共识[J].医药导报, 2021, 40(1): 1-19.
[21]	Gool JDV, Hirche H, Lax H, et al. Folic acid and primary prevention of neural tube defects: a review[J]. Reprod Toxicol, 2018, 80: 73-84.
[22]	Ebbing M, Bønaa KH, Nygård O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12[J]. JAMA, 2009, 302(19): 2119-2126.
[23]	Zhang Q, Wu H, Zou M, et al. Folic acid improves abnormal behavior via mitigation of oxidative stress, inflammation, and ferroptosis in the BTBR T+ tf/J mouse model of autism[J]. J Nutr Biochem, 2019, 71: 98-109.
[24]	Shi Y, Huang C, Yi H, et al. RIPK3 blockade attenuates kidney fibrosis in a folic acid model of renal injury[J]. FASEB J, 2020, 34(8): 10286-10298.

Please choose a citation manager

Content to export