PMID- 12124426 OWN - NLM STAT- MEDLINE DCOM- 20020806 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 82 IP - 2 DP - 2002 Jul TI - Expression of CD47/integrin-associated protein induces death of cultured cerebral cortical neurons. PG - 249-57 AB - The death and survival of neuronal cells are regulated by various signaling pathways during development of the brain and in neuronal diseases. Previously, we demonstrated that the neuronal adhesion molecule brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1 (BIT/SHPS-1) is involved in brain-derived neurotrophic factor (BDNF)-promoted neuronal cell survival. Here, we report the apoptosis-inducing effect of CD47/integrin-associated protein (IAP), the heterophilic binding partner of BIT/SHPS-1, on neuronal cells. We generated a recombinant adenovirus vector expressing a neuronal form of CD47/IAP, and found that the expression of CD47/IAP by infection with CD47/IAP adenovirus induced the death of cultured cerebral cortical neurons. The numbers of TdT-mediated biotin-dUTP nick-end labelling (TUNEL)-positive neurons and of cells displaying apoptotic nuclei increased by expression of CD47/IAP. Neuronal cell death was prevented by the addition of the broad-spectrum caspase inhibitor Z-VAD-fmk. Furthermore, we observed that co-expression of CD47/IAP with BIT/SHPS-1 enhanced neuronal cell death, and that BDNF prevented it. These results suggest that CD47/IAP is involved in a novel pathway which regulates caspase-dependent apoptosis of cultured cerebral cortical neurons. CD47/IAP-induced death of cultured cortical neurons may be regulated by the interaction of CD47/IAP with BIT/SHPS-1 and by BDNF. FAU - Koshimizu, Hisatsugu AU - Koshimizu H AD - Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Japan. FAU - Araki, Toshiyuki AU - Araki T FAU - Takai, Satomi AU - Takai S FAU - Yokomaku, Daisaku AU - Yokomaku D FAU - Ishikawa, Yasuyuki AU - Ishikawa Y FAU - Kubota, Misae AU - Kubota M FAU - Sano, Shin-ichiro AU - Sano S FAU - Hatanaka, Hiroshi AU - Hatanaka H FAU - Yamada, Masashi AU - Yamada M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation) RN - 0 (CD47 Antigen) RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Neural Cell Adhesion Molecule L1) RN - 0 (Neural Cell Adhesion Molecules) RN - 0 (Receptors, Immunologic) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Antigens, CD/*biosynthesis/genetics/pharmacology MH - *Antigens, Differentiation MH - Apoptosis/drug effects/*physiology MH - CD47 Antigen MH - Carrier Proteins/*biosynthesis/genetics/pharmacology MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/*metabolism MH - Drug Synergism MH - Female MH - Genetic Vectors/genetics/metabolism MH - In Situ Nick-End Labeling MH - Male MH - Membrane Glycoproteins/biosynthesis/genetics/pharmacology MH - *Neural Cell Adhesion Molecule L1 MH - Neural Cell Adhesion Molecules/biosynthesis/genetics/pharmacology MH - Neurons/cytology/drug effects/*metabolism MH - Rats MH - Rats, Wistar MH - *Receptors, Immunologic EDAT- 2002/07/19 10:00 MHDA- 2002/08/07 10:01 CRDT- 2002/07/19 10:00 PHST- 2002/07/19 10:00 [pubmed] PHST- 2002/08/07 10:01 [medline] PHST- 2002/07/19 10:00 [entrez] AID - 10.1046/j.1471-4159.2002.00965.x [doi] PST - ppublish SO - J Neurochem. 2002 Jul;82(2):249-57. doi: 10.1046/j.1471-4159.2002.00965.x.