2. Academic Validation
  3. Vitamin D ameliorates Aeromonas hydrophila-induced iron-dependent oxidative damage of grass carp splenic macrophages by manipulating Nrf2-mediated antioxidant pathway

Vitamin D ameliorates Aeromonas hydrophila-induced iron-dependent oxidative damage of grass carp splenic macrophages by manipulating Nrf2-mediated antioxidant pathway

  • Fish Shellfish Immunol. 2023 Oct 5:142:109145. doi: 10.1016/j.fsi.2023.109145.
Hao Sun 1,  Dan Wang 1,  Jingqi Ren 1,  Jiaxi Liu 1,  Zhe Wang 1,  Xinyan Wang 1,  Anying Zhang 1,  Kun Yang 1,  Mu Yang 2,  Hong Zhou 3
Affiliations

Affiliations

  • 1 School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
  • 2 Centre for Translational Research in Cancer, Sichuan Cancer Hospital & Institute, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
  • 3 School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. Electronic address: zhouhongzh@uestc.edu.cn.
PMID: 37805110 DOI: 10.1016/j.fsi.2023.109145
Abstract

Aeromonas hydrophila (A. hydrophila) is one of major pathogenic bacteria in aquaculture and potentially virulent to grass carp (Ctenopharyngodon idella). As an essential nutrient for fish, vitamin D3 (VD3) has been reported to play a role against oxidative stress, but the exact mechanism remains to be elusive. In this study, we found that A. hydrophila induced ferrugination and macrophage aggregation in the spleen of grass carp. Along this line, using the splenic macrophages as the model, the effects of VD3 on A. hydrophila-caused iron deposition and subsequent injuries were determined. In the context, 1,25D3 (the active form of VD3) significantly reduced cellular free Fe2+, lipid peroxidation and lactic dehydrogenase (LDH) release induced by A. hydrophila in the splenic macrophages, indicating the protective effects of VD3 on A. hydrophila-led to ferroptosis-related injuries. In support of this notion, 1,25D3 was effective in hindering Ferroptosis inducers-stimulated LDH release in the same cells. Mechanically, 1,25D3 enhanced iron export protein (ferroportin1) and Glutathione Peroxidase 4 (GPX4) protein levels, and glutathione (GSH) contents via vitamin D receptor (VDR). Moreover, NF-E2-related factor 2 (Nrf2) pathway mediated the regulation of 1,25D3 on GPX4 protein expression and GSH synthesis. Meanwhile, 1,25D3 maintained the stability of Nrf2 proteins possibly by attenuating its ubiquitination degradation. Furthermore, in vivo experiments showed that 1,25D3 injection could not only improve the survival of fish infected by A. hydrophila, but also enhance GSH amounts and decrease malonaldehyde (MDA) contents and iron deposition in the spleen. In summary, our data for the first time suggest that VD3 is a potential antioxidant in fish to fight against A. hydrophila induced-ferroptotic damages.

Keywords

A. hydrophila; Ferroptosis; Grass carp; Splenic macrophages; Vitamin D3.

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