title: Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells.
abstract: 3,3',5-triiodothyronine (T3) is largely generated from thyroxine (T4) by the catalysis of deiodinases in peripheral tissues. Emerging evidences have indicated its broad participation in regulating various metabolic process via protecting tissues from oxidative stress and improving cellular antioxidant capacity. However, the potential correlation between the oxidative stress and conversion of T4 to T3 is still unclear. In the present study, the effects of T3 and T4 on redox homeostasis in HepG2 cells pre-treated with H2O2 was investigated. It revealed that T3 significantly rescued the apoptotic cell death, consistent with an upregulation of cell antioxidant ability and reduction of ROS accumulation while T4 did not. Afterwards, we examined the enzyme activity and mRNA expression of type 1 5'-deiodianse (DIO1), T3 and rT3 level and found that H2O2 reduced both DIO1 activity and expression in a dose-dependent manner, which consequently declined T3 and rT3 generation. Alpha-lipoic acid (LA) treatment notably restored DIO1 activity, T3 and rT3 level, as well as transcriptional abnormalities of inflammation-associated genes. It suggests that oxidative stress may reduce DIO1 activity by an indirect way like activating cellular inflammatory responses. All these results indicate that the oxidative stress downregulates the conversion of T4 to T3 through DIO1 function in HepG2 cells.
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Kanjun
authors.initials: K
authors.lastname: Chen
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Feiting
authors.initials: F
authors.lastname: Wen
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xingan
authors.initials: X
authors.lastname: Xing
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Tang
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China; The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Shi
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China; The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi 214122, China. Electronic address: lgw@jiangnan.edu.cn.
authors.forename: Guowei
authors.initials: G
authors.lastname: Le
mesh_terms: D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D008063:Thioctic Acid / Q000008:administration & dosage*; D013974:Thyroxine / Q000378:metabolism*; D014285:Triiodothyronine, Reverse / Q000378:metabolism*
chemical_list: D014285:Triiodothyronine, Reverse; D008063:Thioctic Acid; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase; D013974:Thyroxine
keywords: Alpha-lipoic acid; Oxidative stress; Thyroid hormone; Type 1 5′-deiodinase