Potential role of TREM2 in high cholesterol‑induced cell injury and metabolic dysfunction in SH‑SY5Y cells

Qiang Zheng; Yinxiu Han; Min Fan; Xinran Gao; Mengdie Ma; Jingxian Xu; Sen Liu; Jinfang Ge

doi:10.3892/etm.2023.11904

Potential role of TREM2 in high cholesterol‑induced cell injury and metabolic dysfunction in SH‑SY5Y cells

Exp Ther Med. 2023 Mar 22;25(5):205. doi: 10.3892/etm.2023.11904. eCollection 2023 May.

Authors

Qiang Zheng^{1

2

3}, Yinxiu Han^{1

2

3}, Min Fan^{1

2

3}, Xinran Gao^{1

2

3}, Mengdie Ma^{1

2

3}, Jingxian Xu^{1

2

3}, Sen Liu^{1

2

3}, Jinfang Ge^{1

2

3}

Affiliations

¹ School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
² Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, Anhui 230032, P.R. China.
³ The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is an important member of the immunoglobulin family of inflammatory stimulating receptors and is involved in a number of pathophysiological processes. The present study aimed to investigate the role of TREM2 in neurotoxicity induced by high cholesterol levels in SH-SY5Y cells and explore the potential mechanism. SH-SY5Y cells were routinely cultured and stimulated with a range of cholesterol concentrations. Cell viability was assessed using an MTT assay, morphological changes were observed, and the cell cycle distribution was measured using flow cytometry. Lipid deposition was measured by Oil red O staining, and the mRNA and protein expression levels of SRBEP-1 and SRBEP-2 were detected by quantitative PCR and western blotting, respectively. Moreover, the protein expression levels of BDNF, Copine-6, TREM1, TREM2, and key molecules of the Wnt signaling pathways were detected by western blotting. Finally, TREM2 was overexpressed to investigate its potential role in high cholesterol-induced neurotoxicity. The results showed that cell viability was significantly decreased in SH-SY5Y cells stimulated with cholesterol (0.1~100 µM) in a dose- and time-dependent manner. Stimulation with 100 µM cholesterol for 24 h resulted in morphological injuries, increased the proportion of SH-SY5Y cells at G0/G1, the degree of lipid accumulation, and the protein expression levels of sterol regulatory element binding protein (SREBP)1 and SREBP2, markedly decreased the protein expression levels of BDNF, Copine-6, and TREM2, and the p-β-catenin/β-catenin ratio, and increased the expression levels of nesfatin-1, TREM1 and the p-GSK3β/GSK3β ratio. Furthermore, the imbalanced expression of BDNF, Copine-6, nesfatin-1, and p-GSK3β induced by high cholesterol levels was reversed after overexpression of TREM2. These results suggest that a high concentration of cholesterol could induce cell injury and lipid deposition in SH-SY5Y cells and that the underlying mechanism may be associated with imbalanced TREM2 expression.

Keywords: BDNF; Copine-6; SH-SY5Y cells; TREM2; Wnt signaling pathway; cholesterol.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China (grant nos. 81870403 and 81701327), the Top Talents in University of Anhui Province (grant no. gxbjZD2022013), the Scientific Research Promotion Plan of Anhui Medical University (grant no. 2022xkjT009), and the Comprehensive Reform Pilot Project of ‘San Quan Education’ of Anhui Medical University (grant no. 2021xsqyr03).