Tectorigenin protects cell damage in Parkinson's disease model by regulating miR-103a-3p/SHC3 pathway

Qian LI; Zijuan FU; Peng SUN; Yibin CAO

doi:10.16016/j.1000-5404.202106021

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Tectorigenin protects cell damage in Parkinson's disease model by regulating miR-103a-3p/SHC3 pathway

Neurosciences | 更新时间：2026-01-09

- Tectorigenin protects cell damage in Parkinson's disease model by regulating miR-103a-3p/SHC3 pathway
- Journal of Third Military Medical University Vol. 43, Issue 24, Pages: 2625-2632(2021)
- 作者机构：
  
  063000 河北唐山，唐山市工人医院神经内科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202106021
  CLC： R282.71;R285.5;R742.5
- Received：03 June 2021，
  
  Revised：2021-08-19，
  
  Published：30 December 2021
- 稿件说明：
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Qian LI, Zijuan FU, Peng SUN, et al. Tectorigenin protects cell damage in Parkinson's disease model by regulating miR-103a-3p/SHC3 pathway[J]. Journal of Third Military Medical University, 2021, 43(24): 2625-2632.
DOI：

Qian LI, Zijuan FU, Peng SUN, et al. Tectorigenin protects cell damage in Parkinson's disease model by regulating miR-103a-3p/SHC3 pathway[J]. Journal of Third Military Medical University, 2021, 43(24): 2625-2632. DOI： 10.16016/j.1000-5404.202106021.

摘要

目的

探讨鸢尾苷元对帕金森病(Parkinson’s disease，PD)模型细胞损伤的影响，分析其是否与调控miR-103a-3p/含有Src同源结构域2的衔接蛋白3(SHC adaptor protein 3，SHC3)通路有关。

方法

用250 mmol/L的1-甲基-4-苯基吡啶离子(MPP

)诱导PC12建立PD细胞模型。PC12细胞分为对照组、PD组、PD+鸢尾苷元50 μmol/L组、PD+鸢尾苷元100 μmol/L组、PD+鸢尾苷元200 μmol/L组、PD+anti-miR-NC组、PD+miR-103a-3p Inhibitor组、PD+鸢尾苷元+miR-103a-3p mimic组。CCK-8法检测各组细胞活力，流式细胞术分析各组细胞凋亡率，试剂盒检测各组细胞超氧化物歧化酶(superoxide dismutase

SOD)活性、丙二醛(malondialdehyde

MDA)水平以及乳酸脱氢酶(lactate dehydrogenase

LDH)释放量，RT-qPCR检测miR-103a-3p表达，Werstern blot检测SHC3蛋白水平。双荧光素酶报告实验分析miR-103a-3p和SHC3靶向关系。

结果

与对照组比较，PD组PC12细胞活力、SOD活性、SHC3蛋白表达显著降低(

0.05)，凋亡率、MDA水平、LDH释放量、miR-103a-3p表达显著升高(

0.05)。与PD组比较，PD+鸢尾苷元50 μmol/L组、PD+鸢尾苷元100 μmol/L组、PD+鸢尾苷元200 μmol/L组PC12细胞活力、SOD活性、SHC3蛋白表达显著升高(

0.05)，凋亡率、MDA水平、LDH释放量、miR-103a-3p表达显著降低(

0.05)。与PD+anti-miR-NC组比较，PD+miR-103a-3p Inhibitor组PC12细胞活力、SOD活性、SHC3蛋白表达显著升高(

0.05)，凋亡率、MDA水平、LDH释放量显著降低(

0.05)。与PD+鸢尾苷元组比较，PD+鸢尾苷元+miR-103a-3p mimic组PC12细胞活力、SOD活性、SHC3蛋白表达显著降低(

0.05)，凋亡率、MDA水平、LDH释放量显著升高(

0.05)。miR-103a-3p与SHC3直接结合。

结论

鸢尾苷元可保护PD模型细胞凋亡和氧化损伤，其机制与抑制miR-103a-3p/SHC3通路有关。

Abstract

Objective

To investigate the effect of tectorigenin on cell model of Parkinson's disease (PD)

so as to further analyze whether its mechanism is related to the regulation of miR-103a-3p/SHC adaptor protein 3 (SHC3) pathway.

Methods

PC12 cells were treated with 250 mmol/L 1-methyl-4-phenylpyridine ion (MPP

) to establish a PD cell model. Then

the cells were divided into control group and experimental groups as follows: PD group

PD+50 μmol/L tectorigenin

PD+100 μmol/L tectorigenin

PD+200 μmol/L tectorigenin

PD+anti-miR-NC

PD+miR-103a-3p inhibitor

and PD+tectorigenin+miR-103a-3p mimic. Cell viability and apoptotic rate of each group were evaluated using CCK-8 assay and flow cytometry respectively. The activity of superoxide dismutase (SOD)

content of malondialdehyde (MDA) and release of lactate dehydrogenase (LDH) of cells in each group were subsequently detected. Moreover

RT-qPCR and Western blotting were performed to determine the mRNA expression of miR-103a-3p and protein level of SHC3

respectively

and dual luciferase reporting assay was adopted to analyze the targeting relationship between miR-103a-3p and SHC3.

Results

As compared with the control group

the viability

SOD activity

and SHC3 expression of cells were notably reduced (

0.05)

while the apoptotic rate

MDA content

LDH release

and miR-103a-3p expression were significantly increased (

0.05) in the PD group. When compared with the PD group

the viability

SOD activity

and SHC3 expression of cells in the PD+tectorigenin (50

100 and 200 μmol/L) groups were all notably improved (

0.05)

while the apoptotic rate

MDA content

LDH release and miR-103a-3p level were greatly declined (

0.05). In addition

the cell viability

SOD activity and SHC3 level were higher

whereas the apoptotic rate

MDA content and LDH release were lower in the PD+miR-103a-3p inhibitor group than in the PD+anti-miR-NC group (

0.05). Finally

the ce

ll viability

SOD activity and SHC3 expression in the PD+tectorigenin+miR-103a-3p mimic group were notably decreased (

0.05)

while the apoptotic rate

MDA content

and LDH release were increased (

0.05)

as compared with the PD+tectorigenin groups. Dual luciferase reporting assay showed that SHC3 was a direct target of miR-103a-3p.

Conclusion

Tectorigenin protects PD model cells against apoptosis and oxidative damage

which may be related to the inhibition of miR-103a-3p/SHC3 pathway.

关键词

Keywords

references

ELLIS J M, FELL M J. Current approaches to the treatment of Parkinson's disease[J]. Bioorg Med Chem Lett, 2017, 27(18): 4247-4255. DOI: 10.1016/j.bmcl.2017.07.075.

FERRANTE M, CONTI G O. Environment and neurodegene-rative diseases: an update on miRNA role[J]. Microrna, 2017, 6(3): 157-165. DOI: 10.2174/2211536606666170811151503.

RUPAIMOOLE R, SLACK F J. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov, 2017, 16(3): 203-222. DOI: 10.1038/nrd.2016.246.

ZHOU J J, ZHAO Y, LI Z L, et al . MiR-103a-3p regulates mitophagy in Parkinson's disease through Parkin/Ambra1 signaling[J ] . Pharmacol Res, 2020, 160: 105197. DOI: 10.1016/j.phrs.2020.105197.

ULIVIERI C, SAVINO M T, LUCCARINI I, et al . The adap- tor protein rai/ShcC promotes astrocyte-dependent inflammation during experimental autoimmune encephalomyelitis[J ] . J Immunol, 2016, 197(2): 480-490. DOI: 10.4049/jimmunol.1502063.

GONG J, ZHANG L, ZHANG Q, et al . Lentiviral vector-mediated SHC 3 silencing exacerbates oxidative stress injury in nigral dopamine neurons by regulating the PI3K-AKT-FoxO signaling pathway in rats with Parkinson's disease[J ] . Cell Physiol Biochem, 2018, 49(3): 971-984. DOI: 10.1159/000493228..

王金凤, 薄华本, 孟祥颖, 等. 鸢尾苷元对急性心肌梗死小鼠心肌的保护作用[J]. 中国新药与临床杂志, 2010, 29(2): 99-103.

WANG J F, BO H B, MENG X Y, et al . Cardioprotective function of tectorigenin in acute myocardial infarction in mice[J ] . Chin J New Drugs Clin Remedies, 2010, 29(2): 99-103.

ZHANG L, ZHAO Y, FAN L, et al . Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogen-activated protein kinase and TLR4/nuclear factor-κB pathways and autophagy[J ] . Phytother Res, 2019, 33(4): 1055-1064. DOI: 10.1002/ptr.6299.

齐献忠, 邢英瀛, 秦慧兵. 过表达SHC3激活AKT/Nrf2/GSH通路保护帕金森病氧化应激损伤[J]. 中国老年学杂志, 2019, 39(17): 4333-4337.

QI X Z, XING Y Y, QIN H B. Overexpression of SHC3 activates AKT/Nrf2/GSH pathway to protect Parkinson's disease from oxidative stress injury[J]. Chin J Gerontol, 2019, 39(17): 4333-4337.

PARK J S, JUNG J S, JEONG Y H, et al . Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: critical role of hemeoxygenase-1 and NQO1 expression[J ] . J Neurochem, 2011, 119 (5): 909-919. DOI: 10.1111/j.1471-4159.2011.07395.x.

NOH D, CHOI J G, HUH E, et al . Tectorigenin, a flavonoid-based compound of leopard lily rhizome, attenuates UV-B-induced apoptosis and collagen degradation by inhibiting oxidative stress in human keratinocytes[J ] . Nutrients, 2018, 10(12): E1998. DOI: 10.3390/nu10121998.

YAO L, YANG M, ZHANG J, et al . Tectorigenin attenuates the OGD/R-induced HT-2 2 cell damage through regulation of the PI3K/AKT and the PPARγ/NF-κB pathways[J ] . Hum Exp Toxicol, 2021, 40(8): 1320-1331. DOI: 10.1177/0960327121993213.

YANG Y, KONG F C, DING Q Q, et al . Bruceine D elevates Nrf2 activation to restrain Parkinson's disease in mice through suppressing oxidative stress and inflammatory response[J ] . Biochem Biophys Res Commun, 2020, 526(4): 1013-1020. DOI: 10.1016/j.bbrc.2020.03.097.

CHEN X, ZHANG W, SUN L, et al . Tectorigenin protect HUVECs from H 2 O 2 -induced oxidative stress injury by regulating PI3K/Akt pathway[J ] . Tissue Cell, 2021, 68: 101475. DOI: 10.1016/j.tice.2020.101475..

MA C H, LIU J P, QU R, et al . Tectorigenin inhibits the inflammation of LPS-induced acute lung injury in mice[J ] . Chin J Nat Med, 2014, 12(11): 841-846. DOI: 10.1016/s1875-5364(14)60126-6.

LU Q L, MA Z J, DING Y, et al . Circulating miR-103a-3p contributes to angiotensin Ⅱ-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis[J ] . Nat Commun, 2019, 10(1): 2145. DOI: 10.1038/s41467-019-10116-0.

ZHOU Y P, XIA Q. Inhibition of miR-103a-3p suppresses lipopolysaccharide-induced sepsis and liverinjury by regulating FBXW7 expression[J]. Cell Biol Int, 2020, 44(9): 1798-1810. DOI: 10.1002/cbin.11372.

LI J S, HE W L, WANG Y, et al . MiR-103a-3p alleviates oxidative stress, apoptosis, and immune disorder in oxygen-glucose deprivation-treated BV 2 microglial cells and rats with cerebral ischemia-reperfusion injury by targeting high mobility group box 1[J ] . Ann Transl Med, 2020, 8(20): 1296. DOI: 10.21037/atm-20-5856..

CHEN L F, LU Q, DENG F M, et al . MiR-103a-3p could attenuate sepsis-induced liver injury by targeting HMGB1[J ] . Inflammation, 2020, 43(6): 2075-2086. DOI: 10.1007/s10753-020-01275-0.

LIU Y, ZHANG X R, YANG B C, et al . Demethylation-induced overexpression of Shc3 drives c-raf-independent activation of MEK/ERK in HCC[J ] . Cancer Res, 2018, 78(9): 2219-2232. DOI: 10.1158/0008-5472.CAN-17-2432.

AZZALIN A, MORETTI E, ARBUSTINI E, et al . Cell density modulates SHC 3 expression and survival of human glioblastoma cells through Fak activation[J ] . J Neurooncol, 2014, 120(2): 245-256. DOI: 10.1007/s11060-014-1551-x..

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杨琴

漆国栋

伍亚民

王海燕

徐珂

侯科名

江琼

Fei SI

Related Institution

Ward 3 of Department of Critical Care Medicine, Lanzhou University Second Hospital

Second Clinical Medical College of Lanzhou University

Department of Pharmacognosy, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University)

Department of Human Anatomy， Anhui Medical University

Department of Geriatrics and Special Service Medicine， First Affiliated Hospital（Southwest Hospital）， Army Medical University （Third Military Medical University）

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