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A thioredoxin reductase and/or thioredoxin system-based mechanism for antioxidant effects of ambroxol.
Biochimie. 2014 Feb; 97:92-103.B

Abstract

Long-term treatment with ambroxol (ABX), a bronchial expectorant, was found to prevent acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The underlying mechanism remains unclear. To address this, we have investigated the effect of ABX on critical antioxidant proteins thioredoxin (Trx) and thioredoxin reductase (TrxR) that are decreased in patients with AECOPD. Trx, TrxR and NADP(H) form Trx system, which is involved in regulating numerous oxidative stress-related events. In human bronchial epithelial cells, treatment with ABX from 0 to 200 μM gradually increased mRNA and protein levels of TrxR/Trx. At these ABX concentrations, TrxR activity was elevated progressively, whereas Trx activity exhibited a dose-dependent biphasic response, increasing at 50 and 75 μM, but decreasing at ABX over 150 μM. Pre-treatment with 75 μM ABX enhanced the capacity of the cells to eliminate reactive oxygen species, which was largely prevented by knockdown of cytosolic Trx (hTrx1). In a purified system, ABX shortened the initial lag phase during the reduction of insulin disulfide by Trx system. Pre-treatment of NADPH-reduced TrxR with ABX caused a dose- and time-dependent increase in thiolate/selenolate species, i.e. the catalytically active form of TrxR. Kinetic analysis demonstrated that the reduction of H2O2 by TrxR or Trx system were enhanced by 100 or 200 μM ABX. When hTrx1 was mixed with ABX in a molar ratio of 1:1 to 1:100 (which could occur in human plasma), changes in intrinsic Trp fluorescence occurred, and the response of reduced hTrx1 was especially remarkable. These data reveal an ABX-sensing mechanism of TrxR/Trx. We therefore conclude that the antioxidant actions of ABX at physiological concentrations are, at least partially, mediated by TrxR and/or Trx system.

Authors+Show Affiliations

College of Life Sciences, University of Chinese Academy of Sciences, YuQuan Road 19(A), 100049 Beijing, China.Department of Respiratory Medicine, Dayi Hospital Affiliated to Shanxi Medical University, Longcheng Street 99, 030032 Taiyuan, China.School of Public Health, Capital Medical University, 100069 Beijing, China. Electronic address: tianlin@ccmu.edu.cn.College of Life Sciences, University of Chinese Academy of Sciences, YuQuan Road 19(A), 100049 Beijing, China. Electronic address: liazho@ucas.ac.cn.

Pub Type(s)

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

Language

eng

PubMed ID

24103200

Citation

Huang, Jin, et al. "A Thioredoxin Reductase And/or Thioredoxin System-based Mechanism for Antioxidant Effects of Ambroxol." Biochimie, vol. 97, 2014, pp. 92-103.
Huang J, Xu J, Tian L, et al. A thioredoxin reductase and/or thioredoxin system-based mechanism for antioxidant effects of ambroxol. Biochimie. 2014;97:92-103.
Huang, J., Xu, J., Tian, L., & Zhong, L. (2014). A thioredoxin reductase and/or thioredoxin system-based mechanism for antioxidant effects of ambroxol. Biochimie, 97, 92-103. https://doi.org/10.1016/j.biochi.2013.09.024
Huang J, et al. A Thioredoxin Reductase And/or Thioredoxin System-based Mechanism for Antioxidant Effects of Ambroxol. Biochimie. 2014;97:92-103. PubMed PMID: 24103200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A thioredoxin reductase and/or thioredoxin system-based mechanism for antioxidant effects of ambroxol. AU - Huang,Jin, AU - Xu,Jianying, AU - Tian,Lin, AU - Zhong,Liangwei, Y1 - 2013/10/05/ PY - 2013/06/03/received PY - 2013/09/26/accepted PY - 2013/10/10/entrez PY - 2013/10/10/pubmed PY - 2014/8/27/medline KW - 2′,7′-dichlorofluorescin KW - 2′-7′-dichlorodihydrofluorescein diacetate KW - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide KW - 5,5′-dithiobis-(2-nitrobenzoic acid) KW - 5-(iodoacetamido)fluorescein KW - 5-IAF KW - ABX KW - Ambroxol KW - DCF KW - DCFH-DA KW - DTNB KW - DTT KW - Gua HCl KW - MTT KW - PMSF KW - ROS KW - Reactive oxidative species KW - Thioredoxin KW - Thioredoxin reductase KW - Trx KW - TrxR KW - dithiothreitol KW - guanidine hydrochloride KW - phenylmethanesulfonyl fluoride KW - radical oxidative species KW - thioredoxin KW - thioredoxin reductase KW - trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanol, ambroxol SP - 92 EP - 103 JF - Biochimie JO - Biochimie VL - 97 N2 - Long-term treatment with ambroxol (ABX), a bronchial expectorant, was found to prevent acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The underlying mechanism remains unclear. To address this, we have investigated the effect of ABX on critical antioxidant proteins thioredoxin (Trx) and thioredoxin reductase (TrxR) that are decreased in patients with AECOPD. Trx, TrxR and NADP(H) form Trx system, which is involved in regulating numerous oxidative stress-related events. In human bronchial epithelial cells, treatment with ABX from 0 to 200 μM gradually increased mRNA and protein levels of TrxR/Trx. At these ABX concentrations, TrxR activity was elevated progressively, whereas Trx activity exhibited a dose-dependent biphasic response, increasing at 50 and 75 μM, but decreasing at ABX over 150 μM. Pre-treatment with 75 μM ABX enhanced the capacity of the cells to eliminate reactive oxygen species, which was largely prevented by knockdown of cytosolic Trx (hTrx1). In a purified system, ABX shortened the initial lag phase during the reduction of insulin disulfide by Trx system. Pre-treatment of NADPH-reduced TrxR with ABX caused a dose- and time-dependent increase in thiolate/selenolate species, i.e. the catalytically active form of TrxR. Kinetic analysis demonstrated that the reduction of H2O2 by TrxR or Trx system were enhanced by 100 or 200 μM ABX. When hTrx1 was mixed with ABX in a molar ratio of 1:1 to 1:100 (which could occur in human plasma), changes in intrinsic Trp fluorescence occurred, and the response of reduced hTrx1 was especially remarkable. These data reveal an ABX-sensing mechanism of TrxR/Trx. We therefore conclude that the antioxidant actions of ABX at physiological concentrations are, at least partially, mediated by TrxR and/or Trx system. SN - 1638-6183 UR - https://www.unboundmedicine.com/medline/citation/24103200/A_thioredoxin_reductase_and/or_thioredoxin_system_based_mechanism_for_antioxidant_effects_of_ambroxol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-9084(13)00345-3 DB - PRIME DP - Unbound Medicine ER -