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On the Opening of an Insensitive Cyclosporin A Non-specific Pore by Phenylarsine Plus Mersalyl

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Abstract

The purpose of this work was addressed to provide new information on the effect of thiol reagents on mitochondrial non-specific pore opening, and its response to cyclosporin A (CSA). To meet this proposal phenylarsine oxide (PHA) and mersalyl were employed as tools to induce permeability transition and CSA to inhibit it. PHA-induced mitochondrial dysfunction, characterized by Ca2+ efflux, swelling, and membrane de-energization, was inhibited by N-ethylmaleimide and CSA. Conversely, mersalyl failed to inhibit the inducing effect of phenylarsine oxide, it rather strengthened it. In addition, the effect of mersalyl was associated with cross-linking of membrane proteins. The content of membrane thiol groups accessible to react with PHA, mersalyl, and PHA plus mersalyl was determined. In all situations, permeability transition was accompanied by a significant decrease in the whole free membrane thiol content. Interestingly, it is also shown that mersalyl hinders the protective effect of cyclosporin A on PHA-induced matrix Ca2+ efflux.

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Acknowledgments

This work was partially supported by grant 52417/67685 from CONACyT. The authors thank the technical assistance of Mr. Fernando Ibarra.

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  1. Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Col. Sección XVI, Tlalpam, Mexico, D.F., 014080, Mexico

    Noemí García, Eduardo Martínez-Abundis, Natalia Pavón & Edmundo Chávez

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  1. Noemí García
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  2. Eduardo Martínez-Abundis
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  3. Natalia Pavón
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  4. Edmundo Chávez
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Correspondence to Noemí García.

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García, N., Martínez-Abundis, E., Pavón, N. et al. On the Opening of an Insensitive Cyclosporin A Non-specific Pore by Phenylarsine Plus Mersalyl. Cell Biochem Biophys 49, 84–90 (2007). https://doi.org/10.1007/s12013-007-0047-0

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