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Neuronal expression and regulation of rat inhibitor of apoptosis protein-2 by kainic acid in the rat brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Neurobiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Neurobiology)
2002 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 15, no 1, 87-100 p.Article in journal (Refereed) Published
Abstract [en]

Inhibitors of apoptosis proteins (IAPs) define a protein family with the ability to counteract cell death by the inhibition of different caspases activated during apoptosis. These proteins are present in different cells, however, the function and roles of IAPs in brain tissue are not fully understood. We report here that RIAP-2, the rat homologue of human cIAP-1/HIAP-2, is expressed in different areas of rat brain as shown by in situ hybridization and immunohistochemistry. Brain regions with relatively high expression of RIAP-2 mRNA included cortex, cerebellum and different subregions of rat hippocampus. Double labelling using a specific anti-RIAP antibody and markers for neurons and glial cells, showed that RIAP-2 is predominantly expressed by nerve cells. Kainic acid treatment, which induces seizures, transiently up-regulated RIAP-2 mRNA levels in cerebral cortex, in the CA1 and dentate gyrus regions of hippocampus, which returned to normal levels at 24 h. However in the CA3 region, RIAP-2 mRNA was decreased at 6 h following an early up-regulation. This region contains neurons particularly vulnerable to kainic acid induced cell degeneration. The decrease in RIAP-2 following kainic acid was also observed using immunohistochemistry. RIAP-2 protein did not colocalize with TUNEL labelling present in cells undergoing cell death. The results show that in the adult rat brain RIAP-2 is expressed mainly by neurons, and that the levels are regulated by kainic acid, which activates glutamate receptors. The decrease in RIAP-2 in specific neuronal populations may contribute to cell degeneration in vulnerable brain regions observed after kainic acid treatment.

Place, publisher, year, edition, pages
2002. Vol. 15, no 1, 87-100 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89657DOI: 10.1046/j.0953-816x.2001.01847.xPubMedID: 11860509OAI: oai:DiVA.org:uu-89657DiVA: diva2:161322

De två första författarna delar förstaförfattarskapet.

Available from: 2002-02-15 Created: 2002-02-15 Last updated: 2013-05-17Bibliographically approved
In thesis
1. Anti-Apoptotic Proteins in Nerve Cell Survival and Neurodegeneration
Open this publication in new window or tab >>Anti-Apoptotic Proteins in Nerve Cell Survival and Neurodegeneration
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Apoptosis is a genetically regulated cell death program, which shows distinct morphological characteristics. It takes place during neuronal development and in some neurodegenerative diseases. During apoptosis, the intracellular proteins are degraded by various caspases, cysteine aspartases, which are regulated by pro- and anti-apoptotic signals. This thesis elucidates the role of anti-apoptotic proteins in nerve cell survival and neurodegeneration. Studies have focused on Bcl-2 family members and Inhibitor of Apoptosis Proteins (IAP).

XIAP and RIAP-2 are IAP proteins, which are expressed by neurons in the central nervous system. Kainic acid, a glutamate receptor agonist that induces seizures, increased XIAP immunoreactivity in rat hippocampus, whereas RIAP-2 expression in the same time decreased in degenerating neurons. Both XIAP and RIAP-2 were absent in dying neurons indicating that these proteins have a protective role in kainic acid induced neurodegeneration.

NAIP, another IAP family member, was shown to interact with the calcium binding protein Hippocalcin using the yeast two-hybrid system and immunoprecipitation experiments. Hippocalcin-NAIP interaction increased motoneuron survival in caspase-3 independent and dependent manners.

The anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-x, were studied using cultured neurons and human neuronal progenitor cells. In the progenitor cells, Bcl-2 overexpression enhanced cell survival and induced downregulation of Caspase-2 (ICH-1) and caspase-3 (YAMA/CPP32). These results suggest a novel mechanism for the action of Bcl-2.

Estrogen was shown to inhibit death of cultured dorsal root ganglion neurons (DRG) after nerve growth factor withdrawal. The hormone increased the levels of Bcl-x, which may explain the known neuroprotective function of estrogen.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 65 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1120
Neurosciences, neuronal cell death, XIAP, RIAP-2, Hippocalcin, Bcl-2, Bcl-X, kainic acid, DRG, estrogen, Neurovetenskap
National Category
Research subject
Developmental Neurosciences
urn:nbn:se:uu:diva-1752 (URN)91-554-5230-2 (ISBN)
Public defence
2002-03-08, Uppsala Biomedical Centre (BMC), lecture room B22, Uppsala, 09:15
Available from: 2002-02-15 Created: 2002-02-15Bibliographically approved

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