Abstract
The effect of picrotoxin-induced convulsions on lysosomal function in rat brain were evaluated by measuring the free as well as total acid phosphatase, cathepsin D, acid ribonuclease (RNAse II) and acid deoxyribonuclease (DNAse II) activities. Following picrotoxin treatment the free RNAse II activity increased whereas the total activities of practically all the other enzymes decreased. Paradoxically, the cathepsin D activity, free as well the total was completely abolished. In case of all the enzymes the ratio of Total activity/Free activity decreased indicating increased lysosomal membrane fragility which could lead to process of neurodegeneration in the epileptic animals.
Similar content being viewed by others
References
Sloviter, R.S. (1994) The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. Ann. Neurol. 35, 640–654.
Zola-Morgan, S., Squire, L. R. and Amaral, D. G. (1986) Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J. Neurosci. 6, 2950–2967.
Zola-Morgan, S., Squire, L. R., Rempel, N. L. and Amaral D. G. (1992) Enduring memory impairment in monkeys after ischemic damage to the hippocampus. J. Neurosci. 12, 2582–2595.
Singh R. (1980) Lysosomal acid phosphatase hyperactivity in cobalt epilepsy. Ind. J. Exp. Biol. 18, 716–719.
Sangiorgi, S., Ferlini, A., Zanetti, A. and Mochi, M. (1991) Reduced activity of arylsulfatase A and predisposition to neurological disorders: analysis of 140 pediatric patients. Am. J. Med. Genet. 40, 365–369
Tinuper, P., Plazzi, G., Monari, L., Sangiorgi, S., Pellissier, J. F., Cerullo, A., Provini, F., Capellari, S., Baruzzi, A. and Lugaresi, E. (1994) Arylsulfatase A pseudodeficiency and Lafora bodies in a patient with progressive myoclonic epilepsy. Epilepsia 35, 332–335.
Hetman, M., Filipkomski, R. K., Domagala, W. and Kaczmarck, L. (1995) Elevated cathepsin D expresson in kainate-evoked rat brain neurodegeneration. Exptl. Neurol. 136, 53–63.
Houseweart M. K., Pennacchio L. A., Vilaythong A., Peters C., Noebels J. L., Myers R. M. (2003) Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol. 56(4), 315–327.
Rinne R., Saukko P., Jarvinen M., Lehesjoki A. E. (2002) Reduced cystatin B activity correlates with enhanced cathepsin activity in progressive myoclonus epilepsy. Ann Med. 34(5), 380–385.
Mazarati, A. M., Halaszi, E. and Telegdy, G. (1992) Anticonvulsant effects of galanin administrated into the central nervous system upon the picrotoxin-induced seizures syndrome in rats. Brain Res. 589, 164–166.
Kubova, M., Bohuslav, T. and Mares, P. (1992) Effects of clonazepam on picrotoxin induced convulsions. Physiol. Res. 41, 167–169.
Khandkar, M. A., Parmar, D. V., Das, M. and Katyare, S. S. (1996) Is activation of lysosomal enzymes responsible for paracetamol-induced hepatotoxicity and nephrotoxicity? J. Pharm. Pharmacol. 48, 437–440.
Fiske C. H. and Subba Row Y. (1925) Colorimetric detemination of phosphorous. J Biol Chem. 66, 375.
Nerurkar, M. A., Satav, J. G. and Katyare, S. S. (1988) Insulin dependent changes in lysosomal cathepsin D activity in rat liver, kidney, brain and heart. Diabetologia 31, 119–122.
Barret, A. J. and Heath, M. F. (1977) Lysosomal enzymes, In: Lysosomes. A Laboratory handbook. Ed. Dingle, J. T., North Holland, Amsterdam, pp. 19–145.
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. (1951) Protein measurement with Folin phenol reagent. J. Biol. Chem. 193, 265–275.
Koike, M., Nakanishi, H., Saftig, P., Ezaki, J., Isahara, K., Ohsawa, Y., Schulz-Schaeffer, W., Watanabe, T., Waguri, S., Kametaka, S., Shibata, M., Yamamoto, K., Kominami, E., Peters, C., von Figura, K. and Uchiyama, Y. (2000) Cathepsin D deficiency induces lysosomal storage with ceroid lipofuchsin in mouse CNS neurons. J. Neurosci. 20, 6898–6906.
Bernstein, H. G., Keilhoff, G., Kirschke, H., Wiederanders, B., Rinne, A., Khudoerkov, R. and Dorn, A. (1986) Cathepsins B and D in rat brain glia during experimentally induced neuropathological defects. An immunocytochemical approach. Biomed. Biochim. Acta. 45, 1461–1464.
Olszewska, D., Drewa, T., Makarewicz, R. and Drewa, J., Wozniak, A. and Maciak, R. (2001) Significance of cathepsin B and D in physiologic and pathologic processes. Pol. Merkuriusz Lek. 10, 65–70.
Rostislav, K., Petr, B., Frantisek, C. and Oldrich, K. (2001) The cathepsin-D expression in the cytoinvasive stages of coccidia in intestinal mucosa of chickens, and the relevance of this proteinase for intracellular penetration and spreading of coccidian in host tissues. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc Czech Repub. 145, 2001.
Saftig, P., Hartmann, D., Lullmann-Rauch, R., Wolff, J., Evers, M., Koster, A., Hetman, M., von Figura, K. and Peters, C. (1997) Mice deficient in lysosomal acid phosphatase develop lysosomal storage in the kidney and central nervous system. J Biol. Chem. 272, 18628–35.
Tyynela, J., Sohar, I., Sleat, D. E., Gin, R. M., Donnelly, R. J., Baumann, M., Haltia, M. and Lobel, P. (2000) A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration. EMBO J. 19, 2786–92.
Pope, A. and Nixon, R. A. (1984) Proteases of human brain. Brain Res. Rev. 14, 245–278.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Acharya, M.M., Khamesra, S.H. & Katyare, S.S. Picrotoxin-induced convulsions and lysosomal function in the rat brain. Indian J Clin Biochem 20, 56–60 (2005). https://doi.org/10.1007/BF02893043
Issue Date:
DOI: https://doi.org/10.1007/BF02893043