核因子 kappa B（NF-κB）参与了铝诱导的 miR29a/b1 下调。

Nuclear factor kappa B (NF-κB) participates in the aluminum-induced down-regulation of miR29a/b1.

机构信息

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; NHC Key Laboratory of Pneumoconiosis (Shanxi), Medical University, Taiyuan, 030001 Shanxi Province, China.

出版信息

J Trace Elem Med Biol. 2023 Dec;80:127309. doi: 10.1016/j.jtemb.2023.127309. Epub 2023 Sep 21.

DOI:10.1016/j.jtemb.2023.127309

PMID:37801786

Abstract

BACKGROUND

Studies have shown that aluminum (Al) is one of the environmental risk factors leading to Alzheimer's disease (AD), and Al exposure can cause elevated levels of BACE1mRNA, β-secretase (BACE1), and amyloid beta (Aβ) in vivo and in vitro. Previous studies by our research group have shown that this is partly caused by the negative regulation of BACE1 by miRNA29a/b1 (miR29a/b1). Despite the observed the role of nuclear factor kappa B (NF-κB) on many miRNAs, the upstream regulation of NF-κB protein on miR29 remains poorly understood. The purpose of this study was to better define the relationship between NF-κB and miR29a/b1 and the potentially relevant signaling pathways.

METHODS

On the one hand, we constructed the animal model of Al exposure by the intraperitoneal injection of aluminum-maltolate (Al(mal)) in rats. Conversely, NF- κB inhibitors were added to adrenal phaeochromocytoma (PC12) cells exposed to Al(mal).

RESULTS

We verified that NF-κB shows an increasing trend with Al accumulation in the brain of rats, which is accompanied by a downward trend of miR29a/b1. Notably, the suppression of NF-κB significantly increased miR29a/b1 and affected the expression of BACE1mRNA and downstream proteins.

CONCLUSION

Al-induced NF-κB can negatively regulate the expression of miR29a/b1, which then significantly enhances the expression of BACE1 and Aβ plaques.

摘要

背景

研究表明，铝（Al）是导致阿尔茨海默病（AD）的环境风险因素之一，Al 暴露可导致体内和体外 BACE1mRNA、β-分泌酶（BACE1）和淀粉样β（Aβ）水平升高。我们研究小组的先前研究表明，这部分是由于 miRNA29a/b1（miR29a/b1）对 BACE1 的负调控所致。尽管观察到核因子 kappa B（NF-κB）对许多 miRNA 的作用，但 NF-κB 蛋白对 miR29 的上游调控仍知之甚少。本研究旨在更好地定义 NF-κB 和 miR29a/b1 之间的关系以及潜在的相关信号通路。