Effect of KIF5A mediated lysosomal functions in cadmium exposure-induced neurotoxicity <italic style="font-style: italic">in vitro</italic>

Ping DENG; Menyan CHEN; Jia XIE; Li TIAN; Zhengping YU; Huifeng PI

doi:10.16016/j.2097-0927.202108210

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Effect of KIF5A mediated lysosomal functions in cadmium exposure-induced neurotoxicity in vitro

Basic Medicine | 更新时间：2026-01-09

- Effect of KIF5A mediated lysosomal functions in cadmium exposure-induced neurotoxicity in vitro
- Journal of Army Medical University Vol. 44, Issue 4, Pages: 320-328(2022)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)军事预防医学系军队劳动卫生学教研室，电磁辐射医学防护教育部重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82173473);the General Program of National Natural Science Foundation of China(81872596)
- DOI：10.16016/j.2097-0927.202108210
  CLC： R341;R992;R995
- Received：30 August 2021，
  
  Revised：2021-11-12，
  
  Published：28 February 2022
- 稿件说明：
移动端阅览
Ping DENG, Menyan CHEN, Jia XIE, et al. Effect of KIF5A mediated lysosomal functions in cadmium exposure-induced neurotoxicity in vitro[J]. Journal of Army Medical University, 2022, 44(4): 320-328.
DOI：

Ping DENG, Menyan CHEN, Jia XIE, et al. Effect of KIF5A mediated lysosomal functions in cadmium exposure-induced neurotoxicity in vitro[J]. Journal of Army Medical University, 2022, 44(4): 320-328. DOI： 10.16016/j.2097-0927.202108210.

摘要

目的

探讨驱动蛋白家族成员5A(kinesin family member 5A，KIF5A)介导的溶酶体功能损伤在镉神经毒性中的作用。

方法

以原代培养的SPF级C57BL/6J小鼠皮层神经元为模型，分为对照组和镉暴露组。检测氯化镉暴露24 h后皮层神经元的半数抑制浓度(IC

)。进一步用1、2、3 μmol/L氯化镉处理神经元24 h，检测细胞存活率、神经元分化和溶酶体功能。RT-qPCR和Western blot检测KIF5A mRNA和蛋白的表达。腺病毒过表达KIF5A检测镉暴露后神经元的溶酶体功能、分化及细胞存活率。

结果

神经元暴露氯化镉24 h的半数抑制浓度IC

为2.9 μmol/L。与对照组相比，2、3 μmol/L镉暴露24 h后神经元细胞活力受到抑制(

＜0.01)，突起生长的总长度和分枝点数目显著减少(

＜0.01)。此外，与对照组相比，2、3 μmol/L氯化镉处理后显著抑制神经元溶酶体组织蛋白酶B(cathepsin B，CTSB)的活性和改变其酸性环境(

＜0.01)，但是对组织蛋白酶D(cathepsin D，CTSD)活性没有影响。镉暴露后KIF5A的mRNA及蛋白表达显著降低(

＜0.01)。过表达KIF5A可以显著改善镉暴露对神经元组织蛋白酶活性CTSB的抑制、稳定镉暴露造成的溶酶体pH值改变，拮抗镉暴露对神经元细胞活力及突起生长的抑制作用(

＜0.01)。

结论

镉暴露显著减少神经元中KIF5A蛋白的表达，从而损伤溶酶体功能，抑制神经元细胞活力及突起生长。

Abstract

Objective

To investigate the effect of kinesin family member 5A (KIF5A) mediated lysosomal functions in cadmium (Cd) exposure-induced neurotoxicity.

Methods

Primary cortical neurons isolated and primarily cultured from specific pa

thogen free (SPF) C57BL/6J mice were used and divided into control and Cd-exposed groups. The 50% inhibitory concentration (IC

) of cortical neurons after 24 h of Cd exposure was measured. Furthermore

the neurons were treated with 1

2 and 3 μmol/L cadmium chloride (CdCl

) for 24 h

and then cell viability

neuronal differentiation and lysosomal function were measured. RT-qPCR and Western blotting were used to detect the changes of KIF5A expression at mRNA and protein levels. The effects of overexpression of KIF5A by adenoviral vector on cell viability

neuronal differentiation and lysosomal function were also investigated in the Cd-exposed cortical neurons.

Results

The IC

value in neurons exposure to CdCl

for 24 h was determined to be 2.9 μmol/L. Compared with the control group

the cell viability was inhibited (

0.01) and the total length of protrusion growth and the number of branching points were obviously reduced (

0.01) after 2 and 3 μmol/L CdCl

exposure for 24 h. In addition

2 and 3 μmol/L CdCl

treatment also resulted in dramatically decreased lysosomal activity of cathepsin B (CTSB) and altered acidic environment when compared with the control group (

0.01). However

the activity cathepsin D(CTSD) was not significantly changed in CdCl

-exposed neuronal cells. More importantly

the mRNA and protein levels of KIF5A were remarkably decreased after Cd exposure (

0.01). Overexpression of KIF5A effectively increased the CTSB activity

stabilized the lysosomal pH value

and antagonized the inhibitory effect on cell viability and protrusion growth induced by Cd exposure (

0.01).

Conclusion

Cd exposure significantly reduces KIF5A protein expression in neurons

and thereby impairs lysosomal function and inhibits neuronal cell viability and protrusion growth.

关键词

Keywords

references

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Department of Occupational Health， Key Laboratory of Electromagnetic Radiation Protection of Ministry of Education， Faculty of Military Preventive Medicine， Army Medical University （Third Military Medical University）

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⁰

Effect of KIF5A mediated lysosomal functions in cadmium exposure-induced neurotoxicity in vitro

DOI：10.16016/j.2097-0927.202108210

摘要

Abstract

关键词

Keywords

references