In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms

Ohhira, Shuji; Enomoto, Mitsunori; Matsui, Hisao

doi:10.1016/j.tox.2006.08.023

Cited by 32 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because TPT is relatively stable and can be slowly degraded to DPT, MPT, and inorganic tins only by human cytochrome P450 isoforms (Ohhira et al 2006), and because only TPT at 10 μmol/L could cause 50% inhibition of proteasomal activity (Figures 3A, 4A), we believe that most cellular Sn detected in the proteasome immunoprecipitates under our experimental condition (within 2 hr treatment) should be TPT. Therefore, we conclude that the detected Sn represents TPT binding to the proteasome, which is responsible for the decreased proteasomal CT-like activity in the cells.…”

Section: Resultsmentioning

confidence: 94%

The Proteasome Is a Molecular Target of Environmental Toxic Organotins

Shi

Chen

Zhai

et al. 2009

Environ Health Perspect

View full text Add to dashboard Cite

BackgroundBecause of the vital importance of the proteasome pathway, chemicals affecting proteasome activity could disrupt essential cellular processes. Although the toxicity of organotins to both invertebrates and vertebrates is well known, the essential cellular target of organotins has not been well identified. We hypothesize that the proteasome is a molecular target of environmental toxic organotins.ObjectivesOur goal was to test the above hypothesis by investigating whether organotins could inhibit the activity of purified and cellular proteasomes and, if so, the involved molecular mechanisms and downstream events.ResultsWe found that some toxic organotins [e.g., triphenyltin (TPT)] can potently and preferentially inhibit the chymotrypsin-like activity of purified 20S proteasomes and human breast cancer cellular 26S proteasomes. Direct binding of tin atoms to cellular proteasomes is responsible for the observed irreversible inhibition. Inhibition of cellular proteasomes by TPT in several human cell lines results in the accumulation of ubiquitinated proteins and natural proteasome target proteins, accompanied by induction of cell death.ConclusionsThe proteasome is one of the molecular targets of environmental toxic organotins in human cells, and proteasome inhibition by organotins contributes to their cellular toxicity.

show abstract

Section: Resultsmentioning

confidence: 94%

The Proteasome Is a Molecular Target of Environmental Toxic Organotins

Shi

Chen

Zhai

et al. 2009

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…There are sex-and developmental-stagedependent differences in the expression of the CYP2C family in rats (Rich et al, 1997;Mode et al, 1998). However, sex differences in CYP2C metabolism have not been observed in humans (Mugford et al, 1998;Ohhira et al, 2006).…”

Section: Cytochromementioning

confidence: 99%

Anatomical and Physiological Factors Affecting Oral Drug Bioavailability in Rats, Dogs, and Humans

El‐Kattan

Hurst

Brodfuehrer

et al. 2011

Oral Bioavailability

View full text Add to dashboard Cite

“…Detailed characteristics of several CYP3A4 substrates and inhibitors were summarized recently by Liu et al (Liu et al, 2007). The known pesticides mainly metabolized by CYP3A4 belong to several chemical groups such as, carbamate, phosphorothioate, chlorinated cyclodiene and neonicotinoid insecticides (Tang et al, 2002;Abass et al, 2010;Mutch & Williams, 2006;Schulz-Jander & Casida, 2002;Buratti et al, 2005;Sams et al, 2000;Casabar et al, 2006;Mutch et al, 2003;Usmani et al, 2004;Buratti et al, 2002;Buratti et al, 2003;Buratti & Testai, 2007;Butler and Murray, 1997), herbicides (Abass et al, 2007c;Coleman et al, 2000), fungicides (Abass et al, 2007b;Abass et al, 2009;Mazur et al, 2007), and organotin biocide (Ohhira et al, 2006). CYP3A5 mediates midazolam, alprazolam and mifepristone metabolism (Christopher Gorski et al, 1994;Galetin et al, 2004;Hirota et al, 2001;Huang et al, 2004;Khan et al, 2002;Williams et al, 2002).…”

Section: Cyp2e Subfamilymentioning

confidence: 99%