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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Nakano, Mizuho Kanda, Yasunari Yamada, Shigeru Sekino, Yuko Kotake, Yaichiro |
| Copyright Year | 2015 |
| Abstract | Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT acts at the nanomolar level through genomic pathways via the peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR). We recently reported that TBT inhibits cell growth and the ATP content in the human embryonic carcinoma cell line NT2/D1 via a non-genomic pathway involving NAD+-dependent isocitrate dehydrogenase (NAD-IDH), which metabolizes isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we evaluated the effects of TBT on mitochondrial NAD-IDH and energy production. Staining with MitoTracker revealed that nanomolar TBT levels induced mitochondrial fragmentation. TBT also degraded the mitochondrial fusion proteins, mitofusins 1 and 2. Interestingly, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. Incubation with an α-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Our data suggest that nanomolar TBT levels impair mitochondrial quality control via NAD-IDH in NT2/D1 cells. Thus, mitochondrial function in embryonic cells could be used to assess cytotoxicity associated with metal exposure. |
| Starting Page | 1240 |
| Ending Page | 1246 |
| Page Count | 7 |
| File Format | HTM / HTML PDF |
| ISSN | 17565901 |
| Volume Number | 7 |
| Issue Number | 8 |
| Journal | Metallomics |
| DOI | 10.1039/c5mt00033e |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | Estrogen receptor Carcinoma Endocrine system MitoTracker TBT Enzyme inhibitor Cytotoxicity Alpha-Ketoglutaric acid IDH Organotin chemistry Isocitric acid Peroxisome proliferator-activated receptor Retinoid X receptor Apigenin Peroxisome Nicotinamide adenine dinucleotide Tributyltin Adenosine triphosphate |
| Content Type | Text |
| Resource Type | Article |
| Subject | Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics |
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