Browse

Cystamine prevents ischemia-reperfusion injury by inhibiting polyamination of RhoA

Cited 14 time in Web of Science Cited 14 time in Scopus
Authors
Shin, Dong-Myung; Kang, Jinmo; Ha, Jongwon; Kang, Heun-Soo; Park, Sang-Chul; Kim, In-Gyu; Kim, Sang Joon
Issue Date
2007-11-15
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 2008 Jan 18;365(3):509-14
Keywords
AnimalsApoptosis/drug effectsCell LineCold TemperatureCystamine/analysis/*pharmacologyEnzyme Inhibitors/analysis/*pharmacologyGTP-Binding Proteins/*antagonists & inhibitorsL-Lactate DehydrogenaseMyocytes, Cardiac/*drug effects/enzymologyOrgan Preservation Solutions/chemistry/*pharmacologyPolyamines/metabolismRatsReperfusion Injury/*enzymologyTransglutaminases/*antagonists & inhibitorsrho-Associated Kinases/antagonists & inhibitors/metabolismrhoA GTP-Binding Protein/metabolism
Abstract
Transglutaminase2 (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.
ISSN
1090-2104 (Electronic)
0006-291X (Print)
Language
English
URI
http://hdl.handle.net/10371/62872
DOI
https://doi.org/10.1016/j.bbrc.2007.11.007
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Surgery (외과학전공)Journal Papers (저널논문_외과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse