BACKGROUND: Recent clinical trials using @entity2467 + @entity1 cardiac stem cells (CSCs) demonstrated promising results in increasing cardiac function and improving quality of life. However, CSC efficiency is low, likely due to limited cell survival and engraftment after transplantation. The Rho-associated protein kinase (ROCK) inhibitor, @entity12223 , significantly increased cell survival rate, adhesion, and migration in numerous types of cells, including stem cells, suggesting a common feature of the ROCK-mediated apoptotic pathway that may also exist in @entity1 CSCs. In this study, we examine the hypothesis that pretreatment of @entity1 CSCs with @entity12223 protects cells from @entity632 ( @entity3105 ) induced apoptosis. METHODS AND RESULTS: @entity2467 + CSCs were cultured in CSC medium for 3-5 days followed by 48hr treatment with 0 to 10 M @entity12223 alone, 0 to 1.0 M @entity3105 alone, or @entity12223 followed by @entity3105 (48hrs). Cell viability, @entity137 , proliferation, morphology, migration, @entity522 activity, expression levels of apoptotic-related key proteins and @entity2467 + were examined. Results showed that 48hr treatment with @entity12223 alone did not result in great changes in @entity2467 + expression, proliferation, @entity522 activity, or apoptosis; however cell viability was significantly increased and cell migration was promoted. These effects likely involve the ROCK/Actin pathways. In contrast, 48hr treatment with @entity3105 alone dramatically increased @entity522 activity, resulting in cell death. Although @entity12223 alone did not affect the expression levels of apoptotic-related key factors (p- @entity584 , @entity584 , @entity588 , @entity1836 , @entity589 , cleaved @entity522 , and @entity522 ) under basal conditions, it significantly inhibited the @entity3105 -induced increase in cleaved @entity522 and reduced cell death under @entity3105 treatment. CONCLUSIONS: We conclude that preconditioning @entity1 CSCs with @entity12223 significantly reduces @entity3105 -induced cell death and possibly involves the cleaved @entity522 and ROCK/Actin pathways. The beneficial effects of @entity12223 may be applied to stem cell-based therapy to increase cell survival rates after transplantation or to act as a cardiac protective agent for @entity3105 -treated @entity5 @entity1 .

Rho-Associated Kinase Inhibitor ( XXXX ) Attenuates @entity632 -Induced Apoptosis of @entity1 Cardiac Stem Cells.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity632 :: ('MESH:D004317', 'Chemical') :: ['Doxorubicin'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity522 :: ('836', 'Gene') :: ['Caspase-3'] @entity588 :: ('596', 'Gene') :: ['Bcl-2'] @entity589 :: ('581', 'Gene') :: ['Bax'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity1836 :: ('598', 'Gene') :: ['Bcl-xl'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity12223 :: ('MESH:C108830', 'Chemical') :: ['Y-27632'] @entity2467 :: ('3815', 'Gene') :: ['c-kit'] @entity3105 :: ('D004317', 'Chemical') :: ['Dox']
@entity12223 :: (MESH:C108830,Chemical) :: ['Y-27632']
