2,3-Dimercaptopropanol inhibits Ca2+ transport in microsomes from brain but not from fast-skeletal muscle
Ca21 is involved in the regulation of a variety of physiological processes, but a persistent increase in free cytosolic Ca21 concentrations may contribute to cell injury. Dimercaprol (BAL) is a compound used in the treatment of mercury intoxication, but presents low therapeutic efficacy. The molecul...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2001 |
| País: | Brasil |
| Institución: | Universidade Federal do Rio Grande do Sul (UFRGS) |
| Repositorio: | Repositório Institucional da UFRGS |
| Idioma: | inglés |
| OAI Identifier: | oai:www.lume.ufrgs.br:10183/218533 |
| Acceso en línea: | http://hdl.handle.net/10183/218533 |
| Access Level: | acceso abierto |
| Palabra clave: | Dimercaprol Adenosina trifosfatases 2,3- Dimercaptopropanol Ca2+ uptake Ca2+- ATPases |
| Sumario: | Ca21 is involved in the regulation of a variety of physiological processes, but a persistent increase in free cytosolic Ca21 concentrations may contribute to cell injury. Dimercaprol (BAL) is a compound used in the treatment of mercury intoxication, but presents low therapeutic efficacy. The molecular mechanism responsible for the BAL toxicity is poorly known. In the present study, the effect of BAL and inorganic and organic mercury on Ca21 transport by Ca21-ATPases located in the sarco/endoplasmic reticulum of fast-skeletal muscle and brain was examined. Ca21 uptake by brain and fast-skeletal muscle microsomes was inhibited in a dosedependent manner by Hg21. The calculated IC50 for Ca21 uptake inhibition by HgCl2 was 1.05 6 0.09 mM (n 5 8) for brain and 0.72 6 0.06 mM (n 5 9) for muscle. The difference was significant at p , 0.01 (data expressed as mean 6 SD). At a low concentration (1 mM), 2,3-dimercaptopropanol had no effect on Ca21 uptake by brain or muscle vesicles and did not abolish the inhibition caused by Hg21. A high concentration of BAL (1 mM) nearly abolished the inhibition caused by 1.75 mM HgCl2 or 6 mM CH3HgCl in skeletal muscle. Surprisingly, at intermediate concentrations (40–100 mM) BAL partially inhibited Ca21 transport in brain but had no effect on muscle. Furthermore, ATP hydrolysis by brain or muscle microsomes was not inhibited by BAL. These results suggest that in brain microsomes BAL affects in a different way Ca21 transport and ATP hydrolysis. The increase in BAL concentration observed after toxic administration of this compound to experimental animals may contribute to deregulate Ca21 homoeostasis and, consequently, to the neurotoxicity of BAL. |
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