title: Brain infarction correlates more closely with acrolein than with reactive oxygen species.
abstract: Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N(1)-acetyltransferase activity is elevated.
authors.affiliation: 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.forename: Hyerim
authors.initials: H
authors.lastname: Park
authors.forename: Itsuko
authors.initials: I
authors.lastname: Ishii
authors.forename: Madoka
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.forename: Hideki
authors.initials: H
authors.lastname: Tatsukawa
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeguchi
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pegg
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000171:Acrolein / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism
chemical_list: D010743:Phospholipids; D017382:Reactive Oxygen Species; D013096:Spermine; D012313:RNA; D000171:Acrolein