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In vitro effects of inorganic lead on isolated rat brain mitochondrial respiration

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Abstract

The effects of lead acetate on respiration in cerebral and cerebellar mitochondria from immature and adult rats were studied polarographically. With all substrates low lead concentrations produced an increase in respiration. Higher concentrations produced an inhibition of both this lead-induced respiration and ADP-dependent (State 3) respiration. Lead-induced respiration required inorganic phosphate and was inhibited by oligomycin, suggesting a coupling to oxidative phosphorylation. Inhibition of respiration was produced by much lower lead concentrations with NAD-linked citric acid cycle substrates than with succinate or α-glycerophosphate. In partially disrupted mitochondria, NAD-linked substrate oxidation was inhibited at lead concentrations which did not affect NADH oxidation. Thus, in brain mitochondria the NAD-linked dehydrogenases, located in the matrix space, were more sensitive to inhibition by lead than were inner membrane enzymes. All in vitro lead effects on mitochondrial respiration were comparable in cerebral and cerebellar mitochondria isolated from both immature and adult rats.

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References

  1. Pentschew, A., andGarro, T. 1966. Lead encephalomyelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases. Acta Neuropathologica 6:266–278.

    Google Scholar 

  2. Clasen, R. A., Hartmann, J. T., Starr, A. J., Coogan, P. S., Pandolfi, S., Laing, I., Becker, R., andHass, G. M. 1974. Electron microscopic and chemical studies of lead encephalopathy: A comparative study of the human and experimental disease. Am. J. Pathol. 74:215–233.

    Google Scholar 

  3. Holtzman, D., andHsu, J. 1976. Early effects of inorganic lead on immature rat brain mitochondrial respiration. Pediatr. Res. 10:70–75.

    Google Scholar 

  4. Estabrook, R. W. 1967. Mitochondrial respiratory control and the polarographic measurement of ADP/O ratios. Pages 41–47,In Estabrook, R. W., and Pullman, M. C. (eds.), Methods in Enzymology, Vol. X, Academic Press, New York.

    Google Scholar 

  5. Holtzman, S., andMoore, C. L. 1971. A micro-method for the study of oxidative phosphorylation. Biochim. Biophys. Acta 234:1–8.

    Google Scholar 

  6. Slater, E. C. 1967. Applications of inhibitors and uncouplers for a study of oxidative phosphorylation. Pages 48–57,In Estabrook, R. W., and Pullman, M. E. (eds.) Methods in Enzymology, Vol. X, Academic Press, New York.

    Google Scholar 

  7. Chance, B. 1959. Quantitative aspects of the control of oxygen utilization. Pages 91–129,In Walstenholme, G. E. W., and O'Connor, C. M. (eds.), Ciba Foundation Symposium on the Regulation of Cell Metabolism, Little, Brown and Co., Boston.

    Google Scholar 

  8. Chance, B., andWilliams, G. R. 1955. A simple and rapid assay of oxidative phosphorylation. Nature 175:1120–1121.

    Google Scholar 

  9. Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  10. Adam, H. 1965. Adenosine-5′-diphosphate and adenosine-5′-monophosphate. Pages 573–577,In Bergmeyer, H. U. (ed.), Methods in Enzymatic Analysis, Academic Press, New York.

    Google Scholar 

  11. Croxton, F. E. 1953. Elementary Statistics with Applications in Medicine and the Biological Sciences, Dover, New York, pp. 240–242.

    Google Scholar 

  12. Holtzman, D., andMoore, C. L. 1973. Oxidative phosphorylation in immature rat brain mitochondria Biol. Neonate 22:230–242.

    Google Scholar 

  13. Holtzman, D., andMoore, C. L. 1975. Respiration in immature rat brain mitochondria. J. Neurochem. 24:1011–1015.

    Google Scholar 

  14. Holtzman, D., andMagruder, C. S. 1977. Effects of oligomycin on respiration in developing rat brain mitochondria. Brain Research 120:373–378.

    Google Scholar 

  15. Lardy, H. A., Johnson, D., andMacMurray, W. C. 1958. Antibiotics as tools for metabolic studies. I. Survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems. Arch. Biochem. Biophys. 78:587–597.

    Google Scholar 

  16. Lehninger, A. L. 1975. Biochemistry, 2nd Edition, Worth, New York, p. 512.

    Google Scholar 

  17. Cardena, E., Lessler, M. A., andBrierley, G. P. 1969. Inhibition of mitochondrial respiration by lead. J. Cell Biol. 43:16–17A.

    Google Scholar 

  18. Scott, K. M., Hwang, K. M., Jurkowitz, M., andBrierley, G. P. 1971. Ion transport by heart mitochondria. XXIII. The effects of lead on mitochondrial reactions. Arch. Biochem. Biophys. 147:557–567.

    Google Scholar 

  19. Koeppe, D. E., andMiller, R. J. 1970. Lead effects on corn mitochondrial respiration. Science 167:1376–1378.

    Google Scholar 

  20. Dawson, E. B., Cravy, W. D., Clark, R. R., andMcGanity, W. J. 1969. Effect of trace metals on placental metabolism. Am. J. Obstetr. Gynecol. 103:253–256.

    Google Scholar 

  21. Iannaccone, A., Bascolo, P., Bertoli, E., andBombardieri, G. 1974. In vitro effects of lead on enzymatic activities of rabbit kidney mitochondria. Experientia 30:467–468.

    Google Scholar 

  22. Rossi, C. S., andLehninger, A. L. 1963. Stoichiometric relationships between accumulation of ions by mitochondria and the energy-coupling sites in the respiratory chain. Biochemische Z. 338:698–713.

    Google Scholar 

  23. Brierly, G. P., Bachmann, E., andGreen, D. E. 1962. Active transport of inorganic phosphate and magnesium ions by beef heart mitochondria. Proc. Natl. Acad. Sci. 48:1928–1935.

    Google Scholar 

  24. Moore, C. L., andJöbsis, F. F. 1970. Some studies on the control of respiration in rat brain mitochondrial preparations. Arch. Biochem. Biophys. 138:295–305.

    Google Scholar 

  25. Press M. F. 1977. Lead encephalopathy in neonatal Long-Evans rats: Morphologic studies. J. Neuropathol. Exp. Neurol. 34:169–193.

    Google Scholar 

  26. Goldstein, G. W., Asbury, A. K., andDiamond, I. 1974. Pathogenesis of lead encephalopathy. Uptake of lead and reaction of brain capillaries. Arch. Neurol. 31:382–389.

    Google Scholar 

  27. Baltrop, D., Barrett, A. J., andDingle, J. T. 1971. Subcellular distribution of lead in the rat. J. Lab. Clin. Med. 77:705–712.

    Google Scholar 

  28. Castellino, N., andAloj, S. 1969. Intracellular distribution of lead in the liver and kidney of the rat. Br. J. Industr. Med. 26:139–143.

    Google Scholar 

  29. Kochen, J. A., andGreener, Y. 1977. Brain lead levels in hemorrhagic lead encephalopathy. Pediatr. Res. 11:563.

    Google Scholar 

  30. Thomas, J. A., andThomas, I. M. 1974. The pathogenesis of lead encephalopathy. Ind. J. Med. Res. 62:36–41.

    Google Scholar 

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Authors and Affiliations

  1. Departments of Neurology and Pediatrics, Stanford University School of Medicine, 94305, Stanford, California

    D. Holtzman, J. Shen Hsu & P. Mortell

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  1. D. Holtzman
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  2. J. Shen Hsu
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  3. P. Mortell
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Holtzman, D., Hsu, J.S. & Mortell, P. In vitro effects of inorganic lead on isolated rat brain mitochondrial respiration. Neurochem Res 3, 195–206 (1978). https://doi.org/10.1007/BF00964060

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