Peroxiredoxin 6 alleviates high glucose-induced inflammation and apoptosis in HK-2 cells by inhibiting TLR4/NF-κB signaling.

Abstract

Background:

This research sought to elucidate the effects of peroxiredoxin 6 (PRDX6) on the biological processes in diabetic nephropathy (DN) and to identify the underlying regulatory mechanism related to toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling.

Methods:

To induce an in vitro DN cellular model, human kidney 2 (HK-2) cells were treated with high glucose (HG). The mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were then evaluated. After the PRDX6 level had been determined, the effects of its overexpression on the mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were assessed. Next, cytochrome c expression, cell viability, cell apoptosis, the inflammatory level, and the TLR4/NF-κB signaling-related factors were assessed. After the addition of the TLR4 activator CRX-527 or the NF-κB activator phorbol 12-myristate 13-acetate (PMA), cell viability, cell apoptosis and the inflammatory level were evaluated again.

Results:

The results revealed that HG exposure triggered mitochondrial dysfunction and oxidative stress and decreased PRDX6 expression in the HK-2 cells. PRDX6 elevation exacerbated cell viability while alleviating mitochondrial membrane potential loss, oxidative stress, apoptosis, and inflammation in the HG-treated HK-2 cells. Further, PRDX6 inhibited HG-induced TLR4/NF-κB activation. The administration of CRX-527 or PMA reversed the effects of PRDX6 on the cell viability, apoptosis, and inflammation of the HG-exposed HK-2 cells.

Conclusions:

To conclude, PRDX6 appears to protect HG-exposed HK-2 cells against inflammation and apoptosis by inhibiting TLR4/NF-κB signaling.

• Authors: Hao Wu, Rong Wu, Tianxi Liu, Hongbin Ma, Guozhong Xue, Minglong Liu
• Journal: Annals of translational medicine (Ann Transl Med) Vol. 11 Issue 2 Pg. 41 (Jan 31 2023) ISSN: 2305-5839 [Print] China
• PMID: 36819569 (Publication Type: Journal Article)
• Copyright: 2023 Annals of Translational Medicine. All rights reserved.