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Molecular characteristics and induction profiles of hypoxia-inducible factor-1α and other basic helix–loop–helix and Per–Arnt–Sim domain-containing proteins identified in a carcinogenic liver fluke Clonorchis sinensis

Published online by Cambridge University Press:  02 August 2018

Seon-Hee Kim
Affiliation:
Department of Microbiology, Gachon University College of Medicine, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of Korea
Gyu-Seok Oh
Affiliation:
Department of Microbiology, Gachon University College of Medicine, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of Korea
Woon-Mok Sohn
Affiliation:
Department of Parasitology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea
Kihyun Lee
Affiliation:
Department of Systems Biotechnology, Center for Antibiotic Resistome, Chung-Ang University, Anseong 17546, Republic of Korea
Hyun-Jong Yang
Affiliation:
Department of Parasitology, Ewha Womans University School of Medicine, Seoul 03760, Republic of Korea
Young-An Bae*
Affiliation:
Department of Microbiology, Gachon University College of Medicine, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of Korea
*
Author for correspondence: Young-An Bae, E-mail: [email protected]

Abstract

Clonorchis sinensis (C. sinensis), a trematode parasite that invades the hypoxic hepatobiliary tract of vertebrate hosts requires a considerable amount of oxygen for its sexual reproduction and energy metabolism. However, little is known regarding the molecular mechanism of C. sinensis involved in the adaptation to the hypoxic environments. In this study, we investigated the molecular structures and induction patterns of hypoxia-inducible factor-1α (HIF-1α) and other basic helix–loop–helix and Per–Arnt–Sim (bHLH–PAS) domain-containing proteins such as HIF-1β, single-minded protein and aryl hydrocarbon receptor, which might prompt adaptive response to hypoxia, in C. sinensis. These proteins possessed various bHLH–PAS family-specific domains. Expression of C. sinensis HIF-1α (CsHIF-1α) was highly induced in worms which were either exposed to a hypoxic condition or co-incubated with human cholangiocytes. In addition to oxygen, nitric oxide and nitrite affected the CsHIF-1α expression depending on the surrounding oxygen concentration. Treatment using a prolyl hydroxylase-domain protein inhibitor under 20%-oxygen condition resulted in an increase in the CsHIF-1α level. Conversely, the other bHLH–PAS genes were less responsive to these exogenous stimuli. We suggest that nitrite and nitric oxide, as well as oxygen, coordinately involve in the regulation of HIF-1α expression to adapt to the hypoxic host environments in C. sinensis.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2018 

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