Cytotoxicity of tributyltin in rat hippocampal slice cultures

Mizuhashi, Satomi; Ikegaya, Yuji; Matsuki, Norio

doi:10.1016/s0168-0102(00)00137-1

Cited by 51 publications

(38 citation statements)

References 46 publications

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“…4) , 2005); its expression in adult brain cells may therefore sensitise them to certain apoptotic stimuli. An examination of the cells that express Bim in the adult brain may provide an insight into Bim's role in the adult cerebrum, particularly in the CA3, which has been shown to be especially sensitive to brain trauma, protein hyperphosphorylation and endocrine-disruption, (Mizuhashi et al, 2000, Runden et al, 1998, Tashlykov et al, 2007.…”

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confidence: 99%

Key apoptosis regulating proteins are down-regulated during postnatal tissue development

Madden¹,

Donovan²,

Cotter³

2007

Int. J. Dev. Biol.

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The intrinsic apoptotic pathway is essential for murine development. We have previously shown that key mediators of this pathway, such as Bim, Apaf-1 and caspase-3, are down-regulated during the postnatal development of the retina. In this study, we demonstrate that this expression pattern is a feature of other distinct tissues such as the brain, heart and skeletal muscle. Caspase-9 expression is also examined and is shown to follow a different pattern in each tissue. Interestingly, we show that peripheral cells of the internal granular layer of the cerebellum do not down-regulate the intrinsic apoptotic pathway proteins Bim, Apaf-1 or caspase-3. Furthermore, Bim expression is also detectable in the brain stem and the CA3 region of the hippocampus in the adult cerebrum. Finally, we demonstrate that the incidence of TUNEL positive cells in the selected tissues decreases during postnatal development in correlation with the general down-regulation of key apoptotic pathway proteins. In contrast, we also demonstrate that apoptosis persists in the adult thymus and that this tissue continues to express Bim, Apaf-1 and caspase-3 at the same levels as the neonate. In summary, this study shows that a selection of post-mitotic tissues down-regulate key apoptotic proteins, in contrast to the thymus, which requires apoptosis for normal function in early adulthood.

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confidence: 99%

Key apoptosis regulating proteins are down-regulated during postnatal tissue development

Madden¹,

Donovan²,

Cotter³

2007

Int. J. Dev. Biol.

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“…We further found in our current study that TBT induces ER stress-associated apoptosis in cultured PC12 cells by upregulating the Bcl-2 family protein Bim (Figure 4(c)). It has been found previously that TBT induces an excessive increase in Ca 2+ and apoptotic cell death in some types of neuronal cells [12,[62][63][64]. It was also suggested in another report that TBT mobilizes intracellular Ca 2+ in PC12 cells by enhancing the transmembrane influxes of Ca 2+ [65].…”

Section: Discussionmentioning

confidence: 80%

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Sasaya¹,

Yasuzumi²,

Maruoka³

et al. 2012

ABC

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Endocrine-disrupting chemicals (EDCs) are known to exert estrogen-like effects that are similar to those made by naturally produced hormones or by inhibition of the receptors in the cell receiving the hormones. Recently, several reports have indicated that EDCs can affect the developing central nervous system. In our current study, we report that some EDCs induce apoptosis in cultured PC12 cells and can be classified into three groups. Bisphenol A (BPA), pnonylphenol (NP) and tributyltin chloride (TBT) were found to induce endoplasmic reticulum (ER) stress-associated apoptosis and activate the unfolded protein response (UPR) system, whereas benomyl (beno) induced non-ER stress-associated apoptosis. The half-maximal apoptosis-inducing concentrations (IC 50 ) of these EDCs were 160 µM for BPA, 25.6 µM for NP, 640 nM for TBT and 48 µM for beno. Although these concentrations are higher than those found in the environment, some EDCs may have apoptotic effects on various cells in the body, including neurons, through their accumulation in the body over time or condensation through the food chain. On the other hand, benzopyrene, fenvalerate, styrene monomer and bis(2-ethylhexyl)phthalate did not induce apoptosis in PC12 cells. We analyzed also whether apoptosis-inducing EDCs had an estrogen-like effect on cultured PC12 cells transfected with a luciferase reporter plasmid, the activity of which is dependent on estrogen receptor α. We found that BPA had an estrogen-like effect (EC 50 = 5.9 µM) but that NP, TBT and beno did not in transfected PC12 cells. These results suggest that BPA may predominantly exert estrogenic effects, but others may predominantly have apoptosis-inducing effects on cells in the body exposed to a polluted environment.

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“…On the contrary, we observed a dose and time dependant reduction of the inward Ca ++ and Na + currents. Many previous reports have also demonstrated that TBT increases intracellular Ca ++ concentration (Oyama et al 1994;Mizuhashi et al 2000;Nakatsu et al 2006Nakatsu et al , 2007, which, in turn, can induce apoptosis (Chow et al 1992;Corsini et al 1997;Stridh et al 1999). Apoptosis is related to mitochondrion dysfunction, demonstrated by the MTT assay, inducing ATP depletion and Ca ++ release.…”

Section: Discussionmentioning

confidence: 94%

Cultured heart cells from oyster : an experimental approach for evaluation of the toxicity of the marine pollutant tributyltin

Droguet

Devauchelle

Pennec

et al. 2012

Aquat. Living Resour.

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-European Community regulations on chemicals promote alternative methods to test substances presenting potential risks for the environment. In the present work, cultured atrial cells isolated from oyster (Crassostrea gigas) were used as an experimental model to investigate the toxicity of tributyltin (TBT) after short-time exposure at concentrations representative of those that can be measured in seawater, marine sediments and/or bivalves bioaccumulating this pollutant. In vitro and in vivo assays produce values of the same order of magnitude for both animal/cell survival and heart/cardiomyocyte beating rate. The survival rate of whole animals decreased from 10 −6 M TBT after 3 days. For cultured cells, the viability, evaluated using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, significantly decreased after two days of treatment with 10 −6 M TBT, and after six days with 10 −10 M TBT. The percentage of apoptotic cells, quantified by flow cytometry and YO-PRO r -1 iodide, a nucleic acid stain that only permeates cells that are beginning to undergo apoptosis, increased significantly in these cases. Moreover, intracellular concentration of Ca ++ had increased after 10 min of exposition to 10 −6 M, and could be associated with apoptotic processes. As patch clamp experiments showed that Ca ++ conductance was decreased, intracellular calcium increase could mainly be due to a release from internal stores. The decreases in beating rhythm could be explained by the decrease in adenosine triphosphate (ATP) production revealed by 31 P nuclear magnetic resonance (NMR) spectroscopy and confirmed by the increase of the K ATP channel conductance. The related hyperpolarization and the disturbances of the energetic metabolism were clearly related to the loss of the atrial cell contractility and viability.

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Cytotoxicity of tributyltin in rat hippocampal slice cultures

Cited by 51 publications

References 46 publications

Key apoptosis regulating proteins are down-regulated during postnatal tissue development

Key apoptosis regulating proteins are down-regulated during postnatal tissue development

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Cultured heart cells from oyster : an experimental approach for evaluation of the toxicity of the marine pollutant tributyltin

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