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Mitochondrial Glutathione: A Modulator of Brain Cell Death

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Abstract

The small fraction of glutathione in mitochondria in nonneural tissues is an important contributor to cell survival under some conditions. However, there has been only limited characterization of the properties and function of mitochondrial glutathione in cells from the brain. In astrocytes in culture, highly selective depletion of this glutathione pool does not affect cell viability, at least in the first 24 h, but does greatly increase susceptibility to exposure to nitric oxide or peroxynitrite. In vivo, a selective partial loss of glutathione develops during focal cerebral ischemia and persists during reperfusion. The timing and distribution of glutathione loss shows an apparent association with the likelihood that tissue infarction will subsequently develop. Furthermore, infarct volume is greatly decreased by intracerebroventricular infusion of glutathione monoethylester, a compound that can increase mitochondrial glutathione. Together these recent findings indicate that alterations in mitochondrial glutathione are likely to contribute to the severity of tissue damage in stroke and possibly other neurological disorders. Thus, this antioxidant pool provides a potentially useful target for therapeutic intervention.

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REFERENCES

  • Anderson, M. F., Nilsson, M., Eriksson, P. S., and Sims, N. R. (2004a). Neurosci. Lett. 354, 163–165.

    PubMed  Google Scholar 

  • Anderson, M. F., Nilsson, M., and Sims, N. R. (2004b). Neurochem. Int. 44, 153–159.

    PubMed  Google Scholar 

  • Anderson, M. F., and Sims, N. R. (1999). J. Neurochem. 73, 1189–1199.

    PubMed  Google Scholar 

  • Anderson, M. F., and Sims, N. R. (2002). J. Neurochem. 81, 541–549.

    PubMed  Google Scholar 

  • Chen, Z., and Lash, L. H. (1998). J. Pharmacol. Exp. Ther. 285, 608–618.

    PubMed  Google Scholar 

  • Colell, A., Coll, O., Garcia-Ruiz, C., Paris, R., Tiribelli, C., Kaplowitz, N., and Fernandez-Checa, J. C. (2001). Hepatology 34, 964–971.

    PubMed  Google Scholar 

  • Colell, A., Garcia-Ruiz, C., Miranda, M., Ardite, E., Mari, M., Morales, A., Corrales, F., Kaplowitz, N., and Fernandez-Checa, J. C. (1998). Gastroenterology 115, 1541–1551.

    PubMed  Google Scholar 

  • Coll, O., Colell, A., Garcia-Ruiz, C., Kaplowitz, N., and Fernandez-Checa, J. C. (2003). Hepatology 38, 692–702.

    PubMed  Google Scholar 

  • Dhanboora, L. M., and Babson, J. R. (1992). Arch. Biochem. Biophys. 293, 130–139.

    PubMed  Google Scholar 

  • Dringen, R. (2000). Prog. Neurobiol. 62, 649–671.

    PubMed  Google Scholar 

  • Eliasson, M. J., Huang Z., Ferrante, R. J., Sasamata, M., Molliver, M. E., Snyder, S. H., and Moskowitz, M. A. (1999). J. Neurosci. 19, 5910–5918.

    PubMed  Google Scholar 

  • Fernandez-Checa, J. C., Garcia-Ruiz, C., Ookhtens, M., and Kaplowitz, N. (1991). J. Clin. Invest. 87, 397–405.

    PubMed  Google Scholar 

  • Folbergrova, J., Memezawa, H., Smith, M.-L., and Siesjo, B. K. (1992). J. Cereb. Blood Flow Metab. 12,25–33.

    PubMed  Google Scholar 

  • Folbergrova, J., Zhao, Q., Katsura, K.-I., and Siesjo, B. K. (1995). Proc. Natl. Acad. Sci. 92, 5057–5061.

    PubMed  Google Scholar 

  • Grattagliano, I., Vendemiale, G., and Lauterburg, B. H. (1999). J. Surg. Res. 86,2–8.

    PubMed  Google Scholar 

  • Griffith, O. W., and Meister A. (1985). Proc. Natl. Acad. Sci. 82, 4668–4672

    PubMed  Google Scholar 

  • Huang, J., and Philbert, M. A. (1996). Brain Res. 711, 184–192.

    PubMed  Google Scholar 

  • Kowaltowski, A. J., Castilho, R. F., and Vercesi, A. E. (2001). FEBS Letts. 495,12–15.

    Google Scholar 

  • Kuroda, S., Katsura, K., Hillered, L., Bates, T. E., and Siesjo, B. K. (1996). Neurobiol. Dis. 3, 149–157.

    PubMed  Google Scholar 

  • Lash, L. H., Putt, D. A., and Matherly, L. H. (2002). J. Pharmacol. Exp. Ther. 303, 476–486.

    PubMed  Google Scholar 

  • Lash, L. H., Visarius, T. M., Sall, J. M., Qian, W., and Tokarz, J. J. (1998). J. Pharmacol. Exp. Ther. 303, 476–486.

    Google Scholar 

  • Lipton, P. (1999). Physiol. Rev. 79, 1431–1568.

    PubMed  Google Scholar 

  • Liu, D., Lu, C. B., Wan, R. Q., Auyeng, W. W., and Mattson, M. P. (2002). J. Cereb. Blood Flow Metab. 22, 431–443.

    PubMed  Google Scholar 

  • Martensson, J., Jain, A., Frayer, W., and Meister, A. (1989). Proc. Natl. Acad. Sci. 90, 317–321.

    Google Scholar 

  • Martensson, J., Lai, J., and Meister, A. (1990). Proc. Natl. Acad. Sci. 87, 7185–7189.

    PubMed  Google Scholar 

  • Matsumoto, S., Friberg, H., Ferrand-Drake, M., and Wieloch, T. (1999). J. Cereb. Blood Flow Metab. 19, 736–741.

    PubMed  Google Scholar 

  • Meister, A. (1995). Biochim. Biophys. Acta. 1271,35–42.

    PubMed  Google Scholar 

  • Meredith, M. J., and Reed, D. J. (1982). J. Biol. Chem. 257, 3747–3753.

    PubMed  Google Scholar 

  • Meredith, M. J., and Reed, D. J. (1983). Biochem. Pharmacol. 32, 1383–1388.

    PubMed  Google Scholar 

  • Muyderman, H., Nilsson, M., and Sims, N. R. (2004). Proc. Aust. Neu-rosci. Soc. 15, 34.

    Google Scholar 

  • Muyderman, H., Nilsson, M., and Sims, N. R. (Accepted for publication). J. Neurosci.

  • Nakai, A., Kuroda, S., Kristian, A., and Siesjo, B. K. (1997). Neurobiol. Dis. 4, 288–300.

    PubMed  Google Scholar 

  • Radi, R., Cassina, A., and Hodara, R. (2002). Biol. Chem. 383, 401–409.

    PubMed  Google Scholar 

  • Raza, H., Robin, M. A., Fang, J. K., and Avadhani, N. G. (2002). Biochem. J. 366,45–55.

    PubMed  Google Scholar 

  • Rizzardini, M., Lupi, S., Bernasconi, A., Mangolini, A., and Cantoni, L. (2003). J. Neurol. Sci. 207,51–58.

    PubMed  Google Scholar 

  • Shan, X., Jones, D. P., Hashmi, M., and Anders, M. W. (1993). Chem. Res. Toxicol. 6,75–81.

    PubMed  Google Scholar 

  • Shimuzu, K., Lacza, Z., Rajapakse, N., Horiguchi, T., Snipes, J., and Busija, D. W. (2002). Am. J. Physiol. 283, H1005–H1011.

    Google Scholar 

  • Sims, N. R., and Anderson, M. F. (2002). Neurochem. Int. 40, 511–526.

    PubMed  Google Scholar 

  • Wallin, C., Puka-Sundvall, M., Hagberg, H., Weber, S. G., and Sandberg, M. (2000). Dev. Brain Res. 125,51–60.

    Google Scholar 

  • Wullner, U., Seyfried, J., Groscurth, P., Beinroth, S., Winter, S., Gleichmann, M., Heneka, M., Loschmann, P., Schulz, J. B., Weller, M., and Klockgether, T. (1999). Brain Res. 826,53–62.

    PubMed  Google Scholar 

  • Yoshimoto, T., and Siesjö, B. K. (1999). Brain Res. 839, 283–291.

    PubMed  Google Scholar 

  • Zhao, P., Kalhorn, T. F., and Slattery, J. T. (2002). Hepatology 36, 326–335.

    PubMed  Google Scholar 

  • Zheng, Z., Leem, J. E., and Yenari, M. A. (2003). Curr. Mol. Med. 3, 361–372.

    PubMed  Google Scholar 

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Sims, N.R., Nilsson, M. & Muyderman, H. Mitochondrial Glutathione: A Modulator of Brain Cell Death. J Bioenerg Biomembr 36, 329–333 (2004). https://doi.org/10.1023/B:JOBB.0000041763.63958.e7

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