Derlin-1 modulated endoplasmic reticulum stress and apoptosis in Acipenser schrenckii hepatocytes under titanium dioxide nanoparticle exposure

Zhou Zhou; Junquan Zhu; Xuebin Zheng; Tianxun Luo; Shenghan Lv

doi:10.1016/j.aquatox.2025.107467

Derlin-1 modulated endoplasmic reticulum stress and apoptosis in Acipenser schrenckii hepatocytes under titanium dioxide nanoparticle exposure

Aquat Toxicol. 2025 Jun 19:286:107467. doi: 10.1016/j.aquatox.2025.107467. Online ahead of print.

Authors

Zhou Zhou¹, Junquan Zhu², Xuebin Zheng², Tianxun Luo³, Shenghan Lv³

Affiliations

¹ Guizhou Fisheries Research Institute, Guizhou Academy of Agriculture Sciences, Guiyang, China; Guizhou Provincial Special Aquatic Products Engineering Technology Center, Guiyang, China. Electronic address: zz1126277@163.com.
² Key Laboratory of Aquacultural Biotechnology Ministry of Education, and Key Laboratory of Marine Biotechnology of Zhejiang Province, College of Marine Sciences, Ningbo University, Ningbo, China.
³ Guizhou Fisheries Research Institute, Guizhou Academy of Agriculture Sciences, Guiyang, China; Guizhou Provincial Special Aquatic Products Engineering Technology Center, Guiyang, China.

PMID: 40570604
DOI: 10.1016/j.aquatox.2025.107467

Abstract

The wide use of titanium dioxide nanoparticles (TiO₂NPs) has raised environmental concerns, particularly regarding their impact on aquatic organisms and association with endoplasmic reticulum (ER) dysfunction. This study investigates the role of Derlin-1, a key ER-related factor, in mediating ER stress responses under TiO₂NP exposure. We cloned the Derlin-1 coding sequence of Acipenser schrenckii and constructed overexpression and interference recombinant lentiviral vectors targeting Derlin-1. Following vector transfection of A. schrenckii liver tissue (ASL) cells, Derlin-1 expression in the overexpression group was upregulated 7.93-fold, whereas the silencing effect of shRNA1 among the three interfering vectors reached 54.33 %. After 24 h of TiO₂NP exposure, intracellular reactive oxygen species levels were significantly higher in the ASL cell knockdown group than in the overexpression group. Superoxide dismutase, catalase, and glutathione peroxidase activities were significantly lower in the interference group than in the overexpression group, indicating increased oxidative stress. IRE1, ATF6, and PERK expression levels gradually increased, indicating that the unfolded protein response was activated. These levels were significantly higher in the Derlin-1 interference group than in the overexpression group, indicating higher misfolded protein levels in the ER of ASL cells in the interference group. After 24 h of TiO₂NP stress, the Derlin-1 overexpression and interference groups exhibited a significant increase in apoptotic hepatocytes, with a more pronounced elevation observed in the Derlin-1 interference group, indicating that Derlin-1 interference intensified ER stress, thereby promoting cell apoptosis by activating the unfolded protein response. These findings highlight potential targets for reducing TiO₂NP-induced stress in aquatic organisms.

Keywords: Acipenser schrenckii; Derlin-1; ERAD; Interference; Overexpression; TiO(2)-NPs.