Bruce/apollon promotes hippocampal neuron survival and is downregulated by kainic acid.
Prolonged or excess stimulation of excitatory amino acid receptors leads to seizures and the induction of excitotoxic nerve cell injury. Kainic acid acting on glutamate receptors produces degeneration of vulnerable neurons in parts of the hippocampus and amygdala, but the exact mechanisms are not fully understood. We have here investigated whether the anti-apoptotic protein Bruce is involved in kainic acid-induced neurodegeneration. In the rat hippocampus and cortex, Bruce was exclusively expressed by neurons. The levels of Bruce were rapidly downregulated by kainic acid in hippocampal neurons as shown both in vivo and in cell culture. Caspase-3 was activated in neurons exhibiting low levels of Bruce causing cell death. Likewise, downregulation of Bruce using antisense oligonucleotides decreased viability and enhanced the effect of kainic acid in the hippocampal neurons. The results show that Bruce is involved in neurodegeneration caused by kainic acid and the downregulation of the protein promotes neuronal death.
Sokka
Anna-Leena
AL
Medical Research Institute Minerva, Biomedicum Helsinki, Haartmaninkatu 8, FIN-00140 Helsinki, Finland.
Mudo
Guiseppa
G
Aaltonen
Johanna
J
Belluardo
Natale
N
Lindholm
Dan
D
Korhonen
Laura
L
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
D044763:Ubiquitin-Conjugating Enzymes; C506881:Birc6 protein, rat; D007608:Kainic Acid