Apoptotic morphology does not always require caspase activity in rat cerebellar granule neurons

Apoptotic morphology does not always require caspase activity in rat cerebellar granule neurons The death of a cell via apoptosis is characterized by morphological changes including cell shrinkage and nuclear condensation. Intracellularly, proteases, including caspases, are activated. In the present article we have compared the ability of three different neurotoxic agents to induce caspase activity in cerebellar granule cells (CGC). These compounds are the micro-tubule-disrupting agent colchicine and the oxidative stress-inducing agents hydrogen peroxide and meth-ylmercury (MeHg). We have previously shown that each of these agents causes nuclear changes that are consistent with apoptosis, i.e., induction of chromatin condensation and DNA cleavage into fragments of regular size (700, 300 and 50 kbp). However, only colchicine causes a large increase in caspase activity, as monitored by the ability of whole cell extracts to cleave the synthetic caspase substrate DEVD-MCA. In contrast, MeHg and hydrogen peroxide do not induce any significant increase of DEVDase activity as compared to control cells. Immunocytochemistry confirms that active caspase-3 is abundant only in colchicine-exposed cells. In agreement with these findings, the pan-caspase inhibitor, z-VAD-fmk, is efficient in protecting CGC against colchicine, but not against hydrogen peroxide or MeHg. These data suggest that in CGC the activation of caspases is not always required to induce morphological changes and pattern of DNA fragmentation consistent with apoptosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurotoxicity Research Springer Journals

Apoptotic morphology does not always require caspase activity in rat cerebellar granule neurons

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Publisher
Springer Journals
Copyright
Copyright © 2001 by Springer
Subject
Biomedicine; Neurosciences; Pharmaceutical Sciences/Technology; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology
ISSN
1029-8428
eISSN
1476-3524
D.O.I.
10.1007/BF03033206
Publisher site
See Article on Publisher Site

Abstract

The death of a cell via apoptosis is characterized by morphological changes including cell shrinkage and nuclear condensation. Intracellularly, proteases, including caspases, are activated. In the present article we have compared the ability of three different neurotoxic agents to induce caspase activity in cerebellar granule cells (CGC). These compounds are the micro-tubule-disrupting agent colchicine and the oxidative stress-inducing agents hydrogen peroxide and meth-ylmercury (MeHg). We have previously shown that each of these agents causes nuclear changes that are consistent with apoptosis, i.e., induction of chromatin condensation and DNA cleavage into fragments of regular size (700, 300 and 50 kbp). However, only colchicine causes a large increase in caspase activity, as monitored by the ability of whole cell extracts to cleave the synthetic caspase substrate DEVD-MCA. In contrast, MeHg and hydrogen peroxide do not induce any significant increase of DEVDase activity as compared to control cells. Immunocytochemistry confirms that active caspase-3 is abundant only in colchicine-exposed cells. In agreement with these findings, the pan-caspase inhibitor, z-VAD-fmk, is efficient in protecting CGC against colchicine, but not against hydrogen peroxide or MeHg. These data suggest that in CGC the activation of caspases is not always required to induce morphological changes and pattern of DNA fragmentation consistent with apoptosis.

Journal

Neurotoxicity ResearchSpringer Journals

Published: Mar 2, 2009

References

  • Androgen treatment of neonatal rats decreases susceptibility of cerebellar granule neurons to oxidative stress in vitro
    Ahlbom, E.; Grandison, L.; Bonfoco, E.; Zhivotovsky, B.; Ceccatelli, S.
  • Oxidative stress and motor neuron disease
    Cookson, M.R.; Shaw, P.J.
  • Cytochromec release and caspase-3 activation during colchicine-induced apoptosis of cerebellar granule cells
    Gorman, A.M.; Bonfoco, E.; Zhivotovsky, B.; Orrenius, S.; Ceccatelli, S.
  • Effect of protease inhibitors on early events of apoptosis
    Hara, S.; Halicka, H.; Bruno, S.; Gong, J.; Traganos, F.; Darzynkiewicz, D.
  • Detection of activated caspase-3 by a cleavage site-directed antiserum during naturally occurring DRG neurons apoptosis
    Kouroku, Y.; Urase, K.; Fujita, E.; Isahara, K.; Ohsawa, Y.; Uchiyama, Y.; Momoi, M.Y.; Momoi, T.
  • Pathways mediating Ca entry in rat cerebellar granule cells following in vitro exposure to methyl mercury
    Marty, M.S.; Atchison, W.D.
  • Procaspase-3 and poly(ADP)ribose polymerase (PARP) are calpain substrates
    McGinnis, K.M.; Gnegy, M.E.; Park, Y.H.; Mukerjee, N.; Wang, K.K.
  • A novel apoptosis-like pathway, independent of mitochondria and caspases, induced by curcumin in human lymphoblastoid T (Jurkat) cells
    Piwocka, K.; Zablocki, K.; Wieckowski, M.R.; Skierski, J.; Feiga, I.; Szopa, J.; Drela, N.; Wojtczak, L.; Sikora, E.

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