Induction of oxidative stress, apoptosis and DNA damage by koumine in Tetrahymena thermophila

Qiao Ye; Chaonan Zhang; Zhenlu Wang; Yongyong Feng; Aiguo Zhou; Shaolin Xie; Qiong Xiang; Enfeng Song; Jixing Zou

doi:10.1371/journal.pone.0212231

Induction of oxidative stress, apoptosis and DNA damage by koumine in Tetrahymena thermophila

PLoS One. 2019 Feb 12;14(2):e0212231. doi: 10.1371/journal.pone.0212231. eCollection 2019.

Authors

Qiao Ye^{1

2}, Chaonan Zhang^{1

2}, Zhenlu Wang^{1

2}, Yongyong Feng^{1

2}, Aiguo Zhou^{1

2}, Shaolin Xie^{1

2}, Qiong Xiang³, Enfeng Song³, Jixing Zou^{1

2}

Affiliations

¹ Healthy Aquaculture Laboratory, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, China.
² Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, China.
³ Department of Traditional Chinese Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Abstract

Koumine is a component of the Chinese medicinal herb Gelsemium elegans and is toxic to vertebrates. We used the ciliate Tetrahymena thermophila as a model to evaluate the toxic effects of this indole alkaloid in eukaryotic microorganisms. Koumine inhibited T. thermophila growth and viability in a dose-dependent manner. Moreover, this drug produced oxidative stress in T. thermophila cells and expressions of antioxidant enzymes were significantly elevated at high koumine levels (p < 0.05). Koumine also caused significant levels of apoptosis (p < 0.05) and induced DNA damage in a dose-dependent manner. Mitophagic vacuoles were present in cells indicating induction of autophagy by this drug. Expression of ATG7, MTT2/4, CYP1 and HSP70 as well as the MAP kinase pathway gene MPK1 and MPK3 were significantly altered after exposed to koumine. This study represents a preliminary toxicological evaluation of koumine in the single celled eukaryote T. thermophila.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Apoptosis / genetics
DNA Damage*
Gene Expression Regulation / drug effects
Indole Alkaloids / pharmacology*
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / genetics
Oxidative Stress / drug effects*
Oxidative Stress / genetics
Protozoan Proteins / biosynthesis
Protozoan Proteins / genetics
Tetrahymena thermophila / genetics
Tetrahymena thermophila / metabolism*

Substances

Indole Alkaloids
Protozoan Proteins
koumine

Grants and funding

This study was supported by the earmarked fund for China Agriculture Research System(CARS-45) to JZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.