Biosensor discovery of thyroxine transport disrupting chemicals

Marchesini, Gerardo; Meimaridou, Anastasia; Haasnoot, W.; Meulenberg, Eline P.; Albertus, Faywell; Mizuguchi, Mineyuki; Takeuchi, Makoto; Irth, H.; Murk, Albertinka J.

doi:10.1016/j.taap.2008.06.014

Cited by 173 publications

(129 citation statements)

References 62 publications

Supporting

Mentioning

125

Contrasting

Order By: Relevance

“…Six monohydroxylated metabolites of BDE-47 have also been shown to have thyroxine transport-disrupting activity (Marchesini et al 2008). In fact, OH-PBDEs showed binding potency for thyroxine-binding globulin (TBG) and trans thyretin (TTR), which are the two major thryroxine transport proteins in human plasma, each carrying 74% and 20% of total T 4 (Cao et al 2010;Marchesini et al 2008).…”

Section: Cyp2b6mentioning

confidence: 99%

“…In fact, OH-PBDEs showed binding potency for thyroxine-binding globulin (TBG) and trans thyretin (TTR), which are the two major thryroxine transport proteins in human plasma, each carrying 74% and 20% of total T 4 (Cao et al 2010;Marchesini et al 2008). In particular, OH-PBDEs have been found to be moderate to strong binders to TTR and slight to moderate binders to TBG (Marchesini et al 2008). Thus, OH-PBDEs are able to compete with the natural hormone T 4 in binding either TTR or TBG (Marchesini et al 2008).…”

Section: Cyp2b6mentioning

confidence: 99%

“…In particular, OH-PBDEs have been found to be moderate to strong binders to TTR and slight to moderate binders to TBG (Marchesini et al 2008). Thus, OH-PBDEs are able to compete with the natural hormone T 4 in binding either TTR or TBG (Marchesini et al 2008). Marchesini et al (2008) reported that the 3-meta-OH group with two adjacent halogens present in 3-OH-BDE-47 provides the optimum structure for binding to TTR.…”

Section: Cyp2b6mentioning

confidence: 99%

“…Thus, OH-PBDEs are able to compete with the natural hormone T 4 in binding either TTR or TBG (Marchesini et al 2008). Marchesini et al (2008) reported that the 3-meta-OH group with two adjacent halogens present in 3-OH-BDE-47 provides the optimum structure for binding to TTR. These authors also reported affinity rankings for TTR (3-OH-BDE-47 > 5-OH-BDE-47 > 6-OH-BDE-47 > 4´-OH-BDE-49) and TBG (6-OH-BDE-47 > 3-OH-BDE-47 > 5-OH-BDE-47 > 4´-OH-BDE-49).…”

Section: Cyp2b6mentioning

confidence: 99%

See 3 more Smart Citations

Biotransformation of BDE-47 to Potentially Toxic Metabolites Is Predominantly Mediated by Human CYP2B6

Feo¹,

Gross²,

McGarrigle³

et al. 2012

Environ Health Perspect

View full text Add to dashboard Cite

Background: Previous studies have indicated that cytochrome P450s (CYPs) are involved in the metabolism of polybrominated diphenyl ether (PBDE) flame retardants in humans, resulting in the formation of hydroxylated PBDEs (OH-PBDEs) that are potentially more toxic than the parent PBDEs. However, the specific enzymes responsible for the formation of OH-PBDEs are unknown. oBjectives: The purposes of this study were to characterize the in vitro metabolism of 2,2´,4,4´-tetra bromo diphenyl ether (BDE-47) by human liver microsomes (HLM) and recombinant human CYPs, and to identify the CYP(s) that are active in the oxidative metabolism of BDE-47. Methods: Recombinant human CYPs (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) were incubated with BDE-47 (20 µM), and the metabolites were measured and charac terized using gas chromatography with tandem mass spectrometry (GC-MS/MS). For kinetic studies, CYP2B6 and pooled human liver microsomes (HLMs) were incubated with BDE-47 (0-60 µM). results: CYP2B6 was the predominant CYP capable of forming six OH-BDEs, including 3-OH- BDE-47, 5-OH-BDE-47, 6-OH-BDE-47, 4-OH-BDE-42, 4´-OH-BDE-49, and a metabolite tenta tively identified as 2´-OH-BDE-66. On the basis of full-scan GC-MS analysis, we hypothesized the formation of two other metabolites: di-OH-tetra-BDE and di-OH-tetrabrominated dioxin. In kinetic studies of BDE-47 metabolism by CYP2B6 and pooled

show abstract

Section: Cyp2b6mentioning

confidence: 99%

Section: Cyp2b6mentioning

confidence: 99%

Section: Cyp2b6mentioning

confidence: 99%

Section: Cyp2b6mentioning

confidence: 99%

See 2 more Smart Citations

Biotransformation of BDE-47 to Potentially Toxic Metabolites Is Predominantly Mediated by Human CYP2B6

Feo¹,

Gross²,

McGarrigle³

et al. 2012

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…166 OH-BDE metabolites produced in rat liver microsomes enriched with CYP2b (i.e., PB-induced) have been found to compete with THs for binding to the plasma transport protein TTR, potentially leading to greater elimination of TH and hypothyroidism. 149,167 Likewise in a recombinant sea bream TTR assay, several parent PBDEs (BDE-28, -49, -47, -99) were shown to be potent inhibitors of T3 binding to TTR, suggesting competitive interferences, while 6-OH-BDE-47 had less affinity for sea bream TTR than T3 or T4.…”

Section: Altered Expression/activity Of Plasma and Cellular Transportersmentioning

confidence: 99%