Transcriptome analysis of Tetrahymena thermophila response to exposure with dihydroartemisinin

Houjun Pan; Meiling Deng; Bin Zhang; Tiantian Fang; Yuguo Liu

doi:10.1016/j.heliyon.2023.e14069

Transcriptome analysis of Tetrahymena thermophila response to exposure with dihydroartemisinin

Heliyon. 2023 Feb 28;9(3):e14069. doi: 10.1016/j.heliyon.2023.e14069. eCollection 2023 Mar.

Authors

Houjun Pan¹, Meiling Deng², Bin Zhang², Tiantian Fang², Yuguo Liu²

Affiliations

¹ Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology of Guangdong Province, Guangzhou, 510380, China.
² School of Public Health, Guangdong Medical University, Dongguan, 523808, China.

Abstract

Dihydroartemisinin (DHA) is a derivative of artemisinin and is toxic to parasites. We used the Tetrahymena thermophila (T. thermophila) as a model to explore DHA toxicity. Results showed that low concentration of DHA (20 μmol/L) promoted cell proliferation, whereas high concentrations of DHA (40-1280 μmol/L) inhibited that. Appearance of nucleus was pycnosis by laser scanning confocal microscope. DHA significantly elevated activities of SOD and GSH-Px (P < 0.01) and MDA was markedly increased at high level but decreased at low level (P < 0.01). Further results of transcriptome in T. thermophila treated with different concentration DHA group (0, 20, 160 μmol/L) showed that differentially expressed genes (DEGs) were involved in oxidation-reduction and metabolism of exogenous substances indicated oxidative stress stimulation. Kyoto Encyclopedia of Genes and Genomes showed that DEGs were involved in the cytochrome P450-mediated metabolism of exogenous substances, glutathione metabolism and ABC transport. Remarkably, DNA replication was significantly enriched in low concentration DHA, energy metabolism related pathways and necrotic process were considerably enriched in high concentration DHA. The results of RT-qPCR of 13 DEGs were the same as that of transcriptome, in which the expression of GST and GPx family genes were significantly altered after exposed to high-DHA group. DHA induced oxidative stress damage through disturbing with energy. However, detoxification pathways in T. thermophila to resist oxidative damage and cell alleviated low concentration DHA stress by regulating antioxidant enzyme. This study provides good practice on pharmacological mechanism of artemisinin-based drugs in antiparasitic.

Keywords: Dihydroartemisinin; Energy metabolism; Oxidative stress; Tetrahymena thermophila; Toxic effects.