Primate neurons show different vulnerability to transient ischemia and response to cathepsin inhibition - PubMed (original) (raw)
. 2002 Sep;104(3):267-72.
doi: 10.1007/s00401-002-0554-4. Epub 2002 May 9.
Affiliations
- PMID: 12172912
- DOI: 10.1007/s00401-002-0554-4
Primate neurons show different vulnerability to transient ischemia and response to cathepsin inhibition
Masaki Yoshida et al. Acta Neuropathol. 2002 Sep.
Abstract
Previously, we reported "calpain-induced leakage of lysosomal enzyme cathepsin" as a mechanism of ischemic neuronal death specific for primates. Cathepsin inhibitors such as CA-074 and E-64c were demonstrated to significantly inhibit hippocampal neuronal death. Pyramidal neurons of the hippocampus, Purkinje cells in the cerebellum, and neurons in the caudate nucleus, outer putamen and cortical III, V layers, are known to be vulnerable to ischemia. However, regional differences of the vulnerability and response to neuroprotectants, have not been studied in detail. Here, the monkey brains undergoing transient ischemia were studied to clarify such regional differences by the microscopic counting of surviving neurons. The dead neurons were characterized by eosinophilic coagulation necrosis without apoptotic bodies. The control postischemic brain without treatment showed surviving neurons in caudate nucleus (55.8%), outer putamen (44.4%), cortical III layer (37.8%), CA4 (35.3%), cortical V layer (34.1%), cerebellum (28.2%), CA3 (24.3%), CA2 (16.2%), and CA1 (2.0%). Only the CA1 showed an almost total neuronal loss. In contrast, a single postictal injection of CA-074 or E-64c led to significant inhibition of postischemic neuronal death in all brain regions studied. Overall, more surviving neurons were seen after E-64c treatment than with CA-074: cerebellum, 91.6% vs 85.6%; CA4, 88.6% vs 77.3%; caudate nucleus, 86.1% vs 89.8%; CA2, 83.6% vs 53.0%; outer putamen, 81.3% vs 87.7%; CA1, 80.1% vs 47.4%; CA3, 79.6% vs 60.3%; cortical layer III, 75.5% vs 67.7%; and cortical layer V, 75.0% vs 65.9%, for E-64c and CA-074, respectively. Cathepsin plays a critical role in ischemic neuronal death, and its inhibitors may protect neurons throughout the brain.
Similar articles
- Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors.
Tsuchiya K, Kohda Y, Yoshida M, Zhao L, Ueno T, Yamashita J, Yoshioka T, Kominami E, Yamashima T. Tsuchiya K, et al. Exp Neurol. 1999 Feb;155(2):187-94. doi: 10.1006/exnr.1998.6988. Exp Neurol. 1999. PMID: 10072294 - Hippocampal CA1 cell loss in a non-human primate model of transient global ischemia: a pilot study.
Hara K, Yasuhara T, Matsukawa N, Maki M, Masuda T, Yu G, Xu L, Tambrallo L, Rodriguez NA, Stern DM, Kawase T, Yamashima T, Buccafusco JJ, Hess DC, Borlongan CV. Hara K, et al. Brain Res Bull. 2007 Sep 14;74(1-3):164-71. doi: 10.1016/j.brainresbull.2007.06.014. Brain Res Bull. 2007. PMID: 17683803 - Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'.
Yamashima T, Kohda Y, Tsuchiya K, Ueno T, Yamashita J, Yoshioka T, Kominami E. Yamashima T, et al. Eur J Neurosci. 1998 May;10(5):1723-33. doi: 10.1046/j.1460-9568.1998.00184.x. Eur J Neurosci. 1998. PMID: 9751144 - Ca2+-dependent proteases in ischemic neuronal death: a conserved 'calpain-cathepsin cascade' from nematodes to primates.
Yamashima T. Yamashima T. Cell Calcium. 2004 Sep-Oct;36(3-4):285-93. doi: 10.1016/j.ceca.2004.03.001. Cell Calcium. 2004. PMID: 15261484 Review. - The role of lysosomal rupture in neuronal death.
Yamashima T, Oikawa S. Yamashima T, et al. Prog Neurobiol. 2009 Dec;89(4):343-58. doi: 10.1016/j.pneurobio.2009.09.003. Epub 2009 Sep 20. Prog Neurobiol. 2009. PMID: 19772886 Review.
Cited by
- Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function.
Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G, Janke E, Lubejko ST, Greig NH, Mattison JA, Duzel E, van Praag H. Moon HY, et al. Cell Metab. 2016 Aug 9;24(2):332-40. doi: 10.1016/j.cmet.2016.05.025. Epub 2016 Jun 23. Cell Metab. 2016. PMID: 27345423 Free PMC article. Clinical Trial. - Molecular Features of CA-074 pH-Dependent Inhibition of Cathepsin B.
Yoon MC, Christy MP, Phan VV, Gerwick WH, Hook G, O'Donoghue AJ, Hook V. Yoon MC, et al. Biochemistry. 2022 Feb 15;61(4):228-238. doi: 10.1021/acs.biochem.1c00684. Epub 2022 Feb 4. Biochemistry. 2022. PMID: 35119840 Free PMC article. - Lysosomal release of cathepsins causes ischemic damage in the rat hippocampal slice and depends on NMDA-mediated calcium influx, arachidonic acid metabolism, and free radical production.
Windelborn JA, Lipton P. Windelborn JA, et al. J Neurochem. 2008 Jul;106(1):56-69. doi: 10.1111/j.1471-4159.2008.05349.x. Epub 2008 Jul 1. J Neurochem. 2008. PMID: 18363826 Free PMC article. - Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders.
Hook V, Yoon M, Mosier C, Ito G, Podvin S, Head BP, Rissman R, O'Donoghue AJ, Hook G. Hook V, et al. Biochim Biophys Acta Proteins Proteom. 2020 Aug;1868(8):140428. doi: 10.1016/j.bbapap.2020.140428. Epub 2020 Apr 17. Biochim Biophys Acta Proteins Proteom. 2020. PMID: 32305689 Free PMC article. Review. - Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage.
Wang J, Tsirka SE. Wang J, et al. Neurocrit Care. 2005;3(1):77-85. doi: 10.1385/NCC:3:1:077. Neurocrit Care. 2005. PMID: 16159103 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous