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Cystamine prevents ischemia-reperfusion injury by inhibiting polyamination of RhoA

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dc.contributor.authorShin, Dong-Myung-
dc.contributor.authorKang, Jinmo-
dc.contributor.authorHa, Jongwon-
dc.contributor.authorKang, Heun-Soo-
dc.contributor.authorPark, Sang-Chul-
dc.contributor.authorKim, In-Gyu-
dc.contributor.authorKim, Sang Joon-
dc.date.accessioned2010-04-09T06:43:42Z-
dc.date.available2010-04-09T06:43:42Z-
dc.date.issued2007-11-15-
dc.identifier.citationBiochem Biophys Res Commun. 2008 Jan 18;365(3):509-14en
dc.identifier.issn1090-2104 (Electronic)-
dc.identifier.issn0006-291X (Print)-
dc.identifier.urihttp://hdl.handle.net/10371/62872-
dc.description.abstractTransglutaminase2 (TGase2) activates Rho-associated kinase (ROCK), an important mediator of ischemia-reperfusion (IR) injury, through polyamination of RhoA. Cystamine, an oxidized dimer of cysteamine inhibits the transamidation activity of TGase2. We examined whether addition of cystamine to an organ preservation solution protects rat cardiomyocyte cells (H9C2) from cell death in IR injury. H9C2 cells were stored under hypoxic conditions at 4 degrees C in laboratory-made preservation solution (SNU) or SNU solution supplemented with cystamine (SNU-C1), and cell preservation in the two solutions was compared by measuring the release of lactate dehydrogenase. The cells were preserved more effectively in SNU-C1 than in SNU solution. Cystamine inhibited the intracellular activity of TGase2 which increased during cold storage or reoxygenation. The inhibition of TGase2 by cystamine reduced the polyamination of RhoA, the interaction between RhoA and ROCK2, and F-actin formation. Cystamine also prevented the activation of caspases during cold storage. These results suggest that addition of cystamine to the organ preservation solution significantly enhances cardiomyocytes preservation apparently by inhibiting TGase2-mediated RhoA-ROCK pathway and that TGase2 may play an important role in IR injury by regulating ROCK.en
dc.description.sponsorshipThis study was supported by a Grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea(Project No. A040004).en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectAnimalsen
dc.subjectApoptosis/drug effectsen
dc.subjectCell Lineen
dc.subjectCold Temperatureen
dc.subjectCystamine/analysis/*pharmacologyen
dc.subjectEnzyme Inhibitors/analysis/*pharmacologyen
dc.subjectGTP-Binding Proteins/*antagonists & inhibitorsen
dc.subjectL-Lactate Dehydrogenaseen
dc.subjectMyocytes, Cardiac/*drug effects/enzymologyen
dc.subjectOrgan Preservation Solutions/chemistry/*pharmacologyen
dc.subjectPolyamines/metabolismen
dc.subjectRatsen
dc.subjectReperfusion Injury/*enzymologyen
dc.subjectTransglutaminases/*antagonists & inhibitorsen
dc.subjectrho-Associated Kinases/antagonists & inhibitors/metabolismen
dc.subjectrhoA GTP-Binding Protein/metabolismen
dc.titleCystamine prevents ischemia-reperfusion injury by inhibiting polyamination of RhoAen
dc.typeArticleen
dc.contributor.AlternativeAuthor신동명-
dc.contributor.AlternativeAuthor강진모-
dc.contributor.AlternativeAuthor하종원-
dc.contributor.AlternativeAuthor강현수-
dc.contributor.AlternativeAuthor박상철-
dc.contributor.AlternativeAuthor김인규-
dc.contributor.AlternativeAuthor김상준-
dc.identifier.doi10.1016/j.bbrc.2007.11.007-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Surgery (외과학전공)Journal Papers (저널논문_외과학전공)
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