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Caspase-3 cleavage and nuclear localization of caspase-activated DNase in human temporal lobe epilepsy.
J Cereb Blood Flow Metab. 2006 Apr; 26(4):583-9.JC

Abstract

Programmed cell death (apoptosis) signaling pathways have been implicated in seizure-induced neuronal death and the pathogenesis of human temporal lobe epilepsy (TLE). End-stage DNA fragmentation during cell death may be mediated by nucleases including caspase-activated DNase (CAD), apoptosis-inducing factor (AIF) and endonuclease G. In the present study, we investigated the subcellular localization of these nucleases in resected hippocampus from TLE patients and autopsy controls. Subcellular fractionation determined levels of CAD were significantly higher in the nuclear fraction of TLE samples compared with controls, and semiquantitative immunohistochemistry revealed cleaved caspase-3 positive cells in TLE sections but not controls. While mitochondrial levels of AIF and endonuclease G were higher in TLE samples than controls, nuclear localization of AIF was limited and restricted to cells that were negative for cleaved caspase-3. Nuclear accumulation of endonuclease G was not found in TLE samples. These data support ongoing caspase-dependent apoptosis signaling in human TLE and suggest that interventions targeting such pathways may have potential as adjunctive neuroprotective therapy in epilepsy.

Authors+Show Affiliations

Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16121124

Citation

Schindler, Clara K., et al. "Caspase-3 Cleavage and Nuclear Localization of Caspase-activated DNase in Human Temporal Lobe Epilepsy." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 26, no. 4, 2006, pp. 583-9.
Schindler CK, Pearson EG, Bonner HP, et al. Caspase-3 cleavage and nuclear localization of caspase-activated DNase in human temporal lobe epilepsy. J Cereb Blood Flow Metab. 2006;26(4):583-9.
Schindler, C. K., Pearson, E. G., Bonner, H. P., So, N. K., Simon, R. P., Prehn, J. H., & Henshall, D. C. (2006). Caspase-3 cleavage and nuclear localization of caspase-activated DNase in human temporal lobe epilepsy. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 26(4), 583-9.
Schindler CK, et al. Caspase-3 Cleavage and Nuclear Localization of Caspase-activated DNase in Human Temporal Lobe Epilepsy. J Cereb Blood Flow Metab. 2006;26(4):583-9. PubMed PMID: 16121124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caspase-3 cleavage and nuclear localization of caspase-activated DNase in human temporal lobe epilepsy. AU - Schindler,Clara K, AU - Pearson,Erik G, AU - Bonner,Helena P, AU - So,Norman K, AU - Simon,Roger P, AU - Prehn,Jochen H M, AU - Henshall,David C, PY - 2005/8/27/pubmed PY - 2006/6/14/medline PY - 2005/8/27/entrez SP - 583 EP - 9 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 26 IS - 4 N2 - Programmed cell death (apoptosis) signaling pathways have been implicated in seizure-induced neuronal death and the pathogenesis of human temporal lobe epilepsy (TLE). End-stage DNA fragmentation during cell death may be mediated by nucleases including caspase-activated DNase (CAD), apoptosis-inducing factor (AIF) and endonuclease G. In the present study, we investigated the subcellular localization of these nucleases in resected hippocampus from TLE patients and autopsy controls. Subcellular fractionation determined levels of CAD were significantly higher in the nuclear fraction of TLE samples compared with controls, and semiquantitative immunohistochemistry revealed cleaved caspase-3 positive cells in TLE sections but not controls. While mitochondrial levels of AIF and endonuclease G were higher in TLE samples than controls, nuclear localization of AIF was limited and restricted to cells that were negative for cleaved caspase-3. Nuclear accumulation of endonuclease G was not found in TLE samples. These data support ongoing caspase-dependent apoptosis signaling in human TLE and suggest that interventions targeting such pathways may have potential as adjunctive neuroprotective therapy in epilepsy. SN - 0271-678X UR - https://www.unboundmedicine.com/medline/citation/16121124/Caspase_3_cleavage_and_nuclear_localization_of_caspase_activated_DNase_in_human_temporal_lobe_epilepsy_ L2 - https://journals.sagepub.com/doi/10.1038/sj.jcbfm.9600219?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -