Ndfip1对铁离子诱导的神经细胞凋亡的抑制作用及其神经保护作用机制

doi:10.13481/j.1671-587X.20210212

Abstract

Abstract: Objective

To observe the inhibitory effect of Nedd4 family interacting protein 1（Ndfip1）overexpression on the apoptosis of nerve cells under the conditions of iron overload， and to explore the protective mechanism of Ndfip1 in nerve cells.

Methods

The SH-SY5Y cells in experimental group were transfected with Ndfip1 plasmid， and the SH-SY5Y cells in control group were transfected with empty plasmid. MTT method was used to determine the survival rates of SH-SY5Y cells in two groups under the condition of iron overload. The levels of reactive oxygen species（ROS） and malondialdehyde （MDA） in the cells in two groups were detected by ROS and MDA detection kits. The expression levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase-3 （caspase-3） proteins in the cells were detected by Western blotting method.

Results

Compared with control group， the survival rate of cells in experimental group was significantly increased （P<0.05）；compared with control group， the fluorescence of cells in experimental group was significantly weakened， indicating that the ROS level was reduced.Compared with control group， the level of MDA in experimental group was significantly reduced（P<0.05）；the expression level of Bcl-2 protein in the cells in experimental group was increased（P<0.05），and the expression levels of Bax protein and caspase-3 protein in the cells in experimental group were decreased（P<0.05）.

Conclusion

Ndfip1 could reduce the apoptosis induced by iron overload， improve the survival rate of nerve cells，and has protective effect on the nerve cells；its mechanism may be related to reducing the oxidative stress response and inhibiting the apoptosis pathway.

Key words: Nedd4 family interacting protein 1, iron, nerve cells, apoptosis, oxidative stress

CLC Number:

R329.3

Zhanqi ZHAO,Chengjin ZHANG,Juan TIAN. Inhibitory effect of Ndfip1 on ferrion-induced neuronal apoptosis and its neuroprotective mechanism[J].Journal of Jilin University(Medicine Edition), 2021, 47(2): 338-343.

Figures/Tables 2

References 25

1	SVOBODOVA H， KOSNAC D， TANILA H， et al. Iron-oxide minerals in the human tissues ［J］. Biometals， 2020， 33（1）： 1-13.
2	WINN N C， VOLK K M， HASTY A H.Regulation of tissue iron homeostasis： the macrophage ‘ferrostat’［J］. JCI Insight， 2020.DOI：10.1172/jci insight.132964. doi: 10.1172/jci insight.132964
3	LARSEN B， BOURQUE J， MOORE T M， et al. Longitudinal development of brain iron is linked to cognition in youth ［J］. J Neurosci， 2020， 40（9）：1810-1818.
4	RODRIGUE K M， DAUGHERTY A M， FOSTER C M， et al. Striatal iron content is linked to reduced fronto-striatal brain function under working memory load［J］. Neuroimage， 2020，210：116544.
5	MUHOBERAC B B， VIDAL R. Iron， ferritin， hereditary ferritinopathy， and neurodegeneration ［J］. Front Neurosci， 2019， 13：1195.
6	JIA Y， DENG H， QIN Q， et al. JWH133 inhibits MPP⁺-induced inflammatory response and iron influx in astrocytes ［J］. Neurosci Lett， 2020， 720： 134779.
7	ASHRAF A， MICHAELIDES C， WALKER T A， et al. Regional distributions of iron， copper and zinc and their relationships with glia in a normal aging mouse model ［J］. Front Aging Neurosci， 2019， 11： 351.
8	CI Y Z， LI H， YOU L H， et al. Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson’s disease ［J］. Neurochem Int， 2020， 134： 104657.
9	TORO-URREGO N， TURNER L F， AVILA-RODRIGUEZ M F. New insights into oxidative damage and iron associated impairment in traumatic brain injury ［J］. Curr Pharm Des， 2020， 25（45）： 4737-4746.
10	DEVOS D， CABANTCHIK Z I， MOREAU C，et al. Conservative iron chelation for neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis［J］. J Neural Transm （Vienna）， 2020， 127（2）：189-203.
11	INGRASSIA R，GARAVAGLIA B，MEMO M.DMT1 expression and iron levels at the crossroads between aging and neurodegeneration［J］.Front Neurosci，2019，13： 575.
12	ALAVI A， MOKHTARI M， HAJATI R， et al. Late-onset mitochondrial membrane protein-associated neuro-degeneration with extensive brain iron deposition ［J］. Mov Disord Clin Pract， 2020， 7（1）： 120-121.
13	DUDKO H V， URBAN V A， DAVIDOVSKII A I， et al. Structure-based modeling of turnover of Bcl-2 family proteins bound to voltage-dependent anion channel 2 （VDAC2）：Implications for the mechanisms of proapoptotic activation of Bak and Bax in vivo ［J］. Comput Biol Chem， 2020， 85： 107203.
14	JI Z， HE R， CHAO T， et al. Chi-miR-143-3p promotes apoptosis of mammary gland epithelial cells from dairy goats by targeting ndfip1 ［J］. DNA Cell Biol， 2019， 38（11）： 1188-1196.
15	GORLA M，SANTIAGO C，CHAUDHARI K， et al. Ndfip proteins target robo receptors for degradation and allow commissural axons to cross the midline in the developing spinal cord［J］. Cell Rep， 2019， 26（12）： 3298-3312.
16	JIANG H， THOMAS S N， CHEN Z， et al. Comparative analysis of the catalytic regulation of NEDD4-1 and WWP₂ ubiquitin ligases［J］. J Biol Chem， 2019，294（46）：17421-17436.
17	TIAN J， ZHENG W， LI X L， et al.Lower expression of Ndfip1 is associated with Alzheimer disease pathogenesis through decreasing DMT1 degradation and increasing iron influx ［J］. Front Aging Neurosci， 2018， 10： 165.
18	田娟，毛建雯. Ndfip1质粒的构建及其在神经母细胞瘤SH-SY5Y细胞中的表达［J］. 吉林大学学报（医学版）， 2019， 45（4）： 825-828.
19	陈明辉，田娟. Ndfip1对神经细胞铁超载损伤的保护作用及机制探讨［J］. 天津医药， 2019， 47（2）： 118-121.
20	BANJARA S， SURAWEERA C D， HINDS M G， et al. The Bcl-2 family： ancient origins， conserved structures， and divergent mechanisms ［J］. Biomolecules， 2020， 10（1）： 128.
21	FU X，FENG Y，SHAO B， et al. Activation of the ERK/Creb/Bcl-2 pathway protects periodontal ligament stem cells against hydrogen peroxide-induced oxidative stress ［J］. Mol Med Rep， 2019， 19（5）： 3649-3657.
22	GHAZIZADEH J， HAMEDEYAZDAN S， TORBATI M， et al.Melissaofficinalis L. hydro-alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis［J］.Exp Physiol， 2020，105（4）：707-720.
23	CHI X K， NGUYEN D， PEMBERTON J M， et al. The carboxyl-terminal sequence of Bim enables Bax activation and killing of unprimed cells［J］.BioRxiv，2019.DOI ：10.1101/554907. doi: 10.1101/554907
24	ROGES C，CRKES D A，NARDONE A， et al.Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation ［J］. Nat Commun， 2019， 10（1）： 1689.
25	CHAUHAN A， KUMAR R， SINGH P， et al.RF hyperthermia by encapsulated Fe₃O₄ nanoparticles induces cancer cell death via time-dependent caspase-3 activation［J］.Nanomedicine （Lond），2020，15（4）： 355-379.

[1]	Xue LUAN,Guanghai YAN,Haibo LI,Bo ZHANG,Wei ZHANG,Yuanyuan HUANG. Effect of salidroside on airway inflammation in mice with asthma and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 537-544.
[2]	Cuilan LIU,Jianjun LI,He JIANG,Jing LIU,Dan WANG,Chen LI,Di ZHAO. Effect of urolithin B on biological behaviors of human glioblastome U118 MG cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 566-574.
[3]	Jia FENG,Haichan XU,Jian WEN,Zehua WU,Yi CHEN. Effect of betulinic acid on proliferation and apoptosis of myeloma cells by regulating JAK2/STAT3 signaling pathway and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 615-622.
[4]	Pei GONG,Jingran LIU,Shimin ZHAO,Yuzhen WANG,Jiming XIE. Inhibitory effect of MCM10 silencing on proliferation of breast cancer MDA-MB-231 cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 652-659.
[5]	Xiaohui LI,Ziwei QU,Xin LU,Qingbin MENG,Huatao CHEN,Jun REN,Chengpei TAN. Regulatory effect of exosomes carrying miR-196b-5p derived from bone marrow mesenchymal stem cells on biological characteristics of colon cancer cells [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 660-668.
[6]	Tianqi ZOU,Lin BAI,Zhengxu ZHANG,He LI,Chunmei WANG,Jinghui SUN,Jianguang CHEN,Xi CHEN,Chengyi ZHANG. Inhibitory effect of prunus tomentosa thunb total flavonoids on skin hypertrophic scar in mice and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 265-274.
[7]	Bingxue QI,Yan MA,Yixian ZHANG,Yadong SUN,Lining MIAO. Effect of liraglutide on expressions of mRNA and protein of related proteins after podocyte injury induced by high glucose and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 275-283.
[8]	Haoxuan TANG,Nanfeng MENG,Meiling DU,Wei WANG,Tao HE. Inhibitory effect of new VEGF monoclonal antibody combined with all-trans retinoic acid on proliferation of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 344-351.
[9]	Jie WU,Xuehua YANG,Ling MA,Wenqiang FAN,Dongdong FU,Xiao GAO,Shufei ZUO,Shu LIANG,Yilu QIN,Peishan WANG,Jinyan GUO. Effect of miR-26a-5p on apoptosis of human rheumatoid arthritis fibroblast-like synovial cells through JAK2/STAT3 signaling pathway [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 460-468.
[10]	Tianye ZHAO,Liting ZHOU,Xueting ZHANG,Wen QI,Xu LI,Shuyue WANG,Lin YE. Analysis on correlation between exposure to air pollutants and hospitalization risk of stroke in Changchun city of Jilin province [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 505-510.
[11]	Haiying ZHANG,Wenxin ZHANG,Wenjing ZHAO,Wei LI. Induction effect of gallic acid on apoptosis of human hepatocellular carcinoma HepG-2 cells through regulating mitochondrial oxidative phosphorylation [J]. Journal of Jilin University(Medicine Edition), 2021, 47(1): 125-132.
[12]	Ruili ZHANG,Xiaoqing YANG,Xiaoge ZHANG,Huafeng GUO,Jihong ZHU. Effect of gestational diabetes mellitus on diaphragmatic function of newborn offsprings of rats [J]. Journal of Jilin University(Medicine Edition), 2021, 47(1): 133-138.
[13]	. Inhibitory effect of curcumin on tumor growth in colorectal cancer mice and its mechanism of PTEN/PI3K/Akt signaling pathwayPEI Yongbin， WANG Guiqi， LI Wei， JIANG Xia， JIANG Haibo， ZHAO Zengren （Department of General Surgery，First Hospital，Hebei Medical University， Shijiazhuang 050031，China） [J]. Journal of Jilin University(Medicine Edition), 2021, 47(1): 145-151.
[14]	Hongfang LI,Shao YANG,Mohan CAO,Lili YUAN,Xiaojin LI,Caixing SHI,Zhuoya WANG,Bailiu YA. Improvement effect of curcumin on cerebral microcirculation disorder in hypercholesterolemia model rats and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(1): 53-58.
[15]	LI Qi, XU Rui, LI Tengteng, JIANG Yichuan, LI Min. Effect of pirarubicin on cardiomyocyte injury in rats and establishment of its model [J]. Journal of Jilin University(Medicine Edition), 2020, 46(05): 948-954.

Inhibitory effect of Ndfip1 on ferrion-induced neuronal apoptosis and its neuroprotective mechanism

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 2

References 25

Related Articles 15

Metrics

Comments

Recommended 10