S-Space College of Medicine/School of Medicine (의과대학/대학원) Surgery (외과학전공) Journal Papers (저널논문_외과학전공)
Cystamine prevents ischemia-reperfusion injury by inhibiting polyamination of RhoA
- Shin, Dong-Myung; Kang, Jinmo; Ha, Jongwon; Kang, Heun-Soo; Park, Sang-Chul; Kim, In-Gyu; Kim, Sang Joon
- Issue Date
- Biochem Biophys Res Commun. 2008 Jan 18;365(3):509-14
- Animals; Apoptosis/drug effects; Cell Line; Cold Temperature; Cystamine/analysis/*pharmacology; Enzyme Inhibitors/analysis/*pharmacology; GTP-Binding Proteins/*antagonists & inhibitors; L-Lactate Dehydrogenase; Myocytes, Cardiac/*drug effects/enzymology; Organ Preservation Solutions/chemistry/*pharmacology; Polyamines/metabolism; Rats; Reperfusion Injury/*enzymology; Transglutaminases/*antagonists & inhibitors; rho-Associated Kinases/antagonists & inhibitors/metabolism; rhoA GTP-Binding Protein/metabolism
- 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.
- 1090-2104 (Electronic)
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