title: Toxic acrolein production due to Ca(2+) influx by the NMDA receptor during stroke.
abstract: OBJECTIVE
  N-Methyl-d-aspartate (NMDA) receptors have a high permeability to Ca(2+), contributing to neuronal cell death after stroke. We recently found that acrolein produced from polyamines is a major toxic compound during stroke. Thus, it was determined whether over-accumulation of Ca(2+) increases the production of acrolein from polyamines in a photochemically-induced thrombosis mouse model of stroke and in cell culture systems.
  
  
  METHODS
  A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. Protein-conjugated acrolein levels at the locus of infarction and in cells were measured by Western blotting. Levels of polyamines were measured by high-performance liquid chromatography.
  
  
  RESULTS
  When the size of brain infarction was decreased by N(1), N(4), N(8)-tribenzylspermidine, a channel blocker of the NMDA receptors, levels of Ca(2+) and protein-conjugated acrolein (PC-Acro) were reduced, while levels of polyamines were increased at the locus of infarction. When cell growth of mouse mammary carcinoma FM3A cells and neuroblastoma Neuro2a cells was inhibited by Ca(2+), the level of polyamines decreased, while that of PC-Acro increased. It was also shown that Ca(2+) toxicity was decreased in an acrolein toxicity decreasing FM3A mutant cells recently isolated. In addition, 20-40 μM Ca(2+) caused the release of polyamines from ribosomes. The results indicate that acrolein is produced from polyamines released from ribosomes through Ca(2+) increase.
  
  
  CONCLUSIONS
  The results indicate that toxicity of Ca(2+) during brain infarction is correlated with the increase of acrolein.
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Saiki
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, 288-0025 Chiba, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Park
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, 288-0025 Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Terui
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, 288-0025 Chiba, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: iga16077@faculty.chiba-u.jp.
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000171:Acrolein / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D000171:Acrolein; D002118:Calcium
keywords: Acrolein; Brain infarction; Ca(2+); Polyamines; Reactive oxygen species; Ribosomes