Neuronal expression and regulation of rat inhibitor of apoptosis protein-2 by kainic acid in the rat brain.
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.
Belluardo
Natale
N
Department of Neuroscience, Neurobiology, Uppsala University, BMC, Box 587, S-751 23 Uppsala, Sweden.
Korhonen
Laura
L
Mudo
Giuseppa
G
Lindholm
Dan
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003001:Cloning, Molecular; D015342:DNA Probes; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats
D015342:DNA Probes; D018076:DNA, Complementary; D018690:Excitatory Amino Acid Agonists; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D012333:RNA, Messenger; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; C494836:Birc3 protein, rat; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D007608:Kainic Acid