Aluminum inhibits non-amyloid pathways via retinoic acid receptor

Huan Li; Qun Liu; Liang Li; Xiujun Qin; ShanShan Wang; Jiali Hu; Xiaoting Lu; Jing Song; JiSheng Nie; Qinli Zhang; Linping Wang; Qiao Niu

doi:10.1016/j.jtemb.2021.126902

Aluminum inhibits non-amyloid pathways via retinoic acid receptor

J Trace Elem Med Biol. 2022 Jan:69:126902. doi: 10.1016/j.jtemb.2021.126902. Epub 2021 Nov 18.

Authors

Huan Li¹, Qun Liu², Liang Li², Xiujun Qin², ShanShan Wang², Jiali Hu², Xiaoting Lu³, Jing Song³, JiSheng Nie³, Qinli Zhang⁴, Linping Wang⁵, Qiao Niu⁶

Affiliations

¹ Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Department of Occupational Health, School of Public Health, Jining Medical University, China.
² Department of Occupational Health, School of Public Health, Shanxi Medical University, China.
³ Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China.
⁴ Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China; Department of Pathology, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
⁵ Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China. Electronic address: sxwlp5945@163.com.
⁶ Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Department of Occupational Health, School of Public Health, Xuzhou Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China. Electronic address: niuqiao55@163.com.

PMID: 34837756
DOI: 10.1016/j.jtemb.2021.126902

Abstract

Background: Aluminium neurotoxicity has been widely confirmed and mainly manifests as cognitive impairment. Al³⁺ can inhibit the expression of ADAM10, a key enzyme of the nonamyloid pathway, but its mechanism of toxicity has not been fully elucidated. Studies have shown that RARs can regulate ADAM10 expression.

Methods: We explored whether Al³⁺ affects the expression of ADAM10 through RARs, thereby affecting the nonamyloid pathway.

Results: Al³⁺ reduced the expressions of RARα, RARβ and ADAM10. The expression levels of the RARα, RARβ and ADAM10 proteins were upregulated in the RA group compared with the control group. In the RA + 200 μmol Al(mal)₃ group, the downregulation of RARα, RARβ and ADAM10 was weaker than that of the 200 μmol Al(mal)₃ group, which indicated that RA participated in and upregulated the expression of ADAM10 through RARα and RARβ.

Conclusion: Al³⁺ inhibits ADAM10 expression through RARα and RARβ and results in a decrease in the nonamyloid pathway.

Keywords: A disintegrin and metalloproteinase 10; Aluminium-maltolate; Non-amyloid pathway; Retinoic acid receptor.

MeSH terms

Aluminum* / toxicity
Receptors, Retinoic Acid*
Retinoic Acid Receptor alpha
Tretinoin

Substances

Receptors, Retinoic Acid
Retinoic Acid Receptor alpha
Tretinoin
Aluminum