Open AccessCharacterization of the Aryl Hydrocarbon Receptor (AhR) Pathway in Anabas testudineus and Mechanistic Exploration of the Reduced Sensitivity of AhR2a
Author(s) -
Wanglong Zhang,
Heidi Qunhui Xie,
Yunping Li,
Xianghui Zou,
Li Xu,
Dan Ma,
Jiao Li,
Yongchao Ma,
Tao Jin,
Mark E. Hahn,
Bin Zhao
Publication year - 2019
Publication title -
environmental science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.851
H-Index - 397
eISSN - 1520-5851
pISSN - 0013-936X
DOI - 10.1021/acs.est.9b04181
Subject(s) - aryl hydrocarbon receptor , anabas testudineus , in silico , cyp1b1 , biology , chemistry , biochemistry , perch , cytochrome p450 , transcription factor , enzyme , gene , fish <actinopterygii> , fishery
Field investigations have revealed the ability of the climbing perch Anabas testudineus to survive in highly contaminated water bodies. The aryl hydrocarbon receptor (AhR) pathway is vital in mediating the toxicity of aromatic hydrocarbon contaminants, and genotypic variation in the AhR can confer resistance to these contaminants. Thus, we characterized the AhR pathway in A. testudineus in order to understand the mechanism(s) underlying the resistance of this species to contaminants and to broaden current knowledge on teleost AhR. In A. testudineus , four AhRs, two AhR nuclear translocators (ARNTs), and one AhR repressor (AhRR) were found. Transient transfection assays revealed that AhR1a, AhR1b, and AhR2b were functional, whereas AhR2a was poorly activated by the potent agonist 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Two ARNTs (partner of AhR) and one AhRR (repressor of AhR) all were functional with each of the active AhR. As a major form, the insensitivity of AhR2a might serve as a potential mechanism for A. testudineus ' reduced sensitivity to severe contamination. We explored the key residues that may account for AhR2a's insensitivity in silico and then functionally validated them in vitro. Two sites (VCS 322-324 , M 370 ) in its ligand-binding domain (LBD) were proved critical for its sensitivity to TCDD. This systematic exploration of the AhR pathway showed that most members have maintained their traditional functions as expected, whereas a nonfunctionalization event has occurred for AhR2a.