Icaritin protects SH-SY5Y cells transfected with TDP-43 by alleviating mitochondrial damage and oxidative stress

Abstract

Background The aim of this study was to investigate the effect of icaritin (ICT) on TAR DNA-binding protein 43 (TDP-43)-induced neuroblastoma (SH-SY5Y) cell damage and to further explore its underlying mechanisms. Methods To investigate the possible mechanism, TDP-43 was used to induce SH-SY5Y cell injury. Cell viability was evaluated by the CCK-8 assay. The mitochondrial membrane potential (MMP) was determined with JC-1. The expression levels of TDP-43 and cytochrome C (CytC) were measuring by Western blotting. Changes in adenosine 5′-triphosphate (ATP) content, total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected with specific kits. Results The results showed that ICT reduced the cell damage induced by TDP-43. ICT reduced the expression level of TDP-43; increased ATP content and the MMP; decreased CytC expression; increased T-AOC and GSH-Px, total SOD (T-SOD), copper/zinc SOD (CuZn-SOD), and manganese SOD (Mn-SOD) activity; and decreased MDA content. Conclusions The results suggest that ICT has a protective effect on TDP-43-transfected SH-SY5Y cells that is related to reductions in TDP-43 expression and mitochondrial damage and alleviation of oxidative stress.

Effect of icaritin on autophagy-related protein expression in TDP-43-transfected SH-SY5Y cells

“…The results of our team suggested that ICT might have potential therapeutic benefits by reducing BACE-1 levels and Aβ 1−42 contents ( Li et al, 2020b ). Our group also suggested that ICT has a protective effect on TDP-induced SH-SY5Y cell injury by reducing TDP-43 expression, mitigating mitochondrial injury and ameliorating oxidative stress ( Zhou et al, 2021 ).…”

“…Previous research by this group has shown that ICT can reduce the neurotoxicity of Aβ and Tau proteins to protect nerve cells ( Feng et al, 2019 ; Feng et al, 2017 ; Li et al, 2021 ). At the same time, ICT reduces the expression of TDP-43 protein by reducing mitochondrial damage and reducing oxidative stress, thereby protecting cells ( Zhou et al, 2021 ).…”