ABSTRACT
Objective To investigate the effects of asymmetric dimethylarginine (ADMA) on apoptosis and phosphorylation of c-jun N-terminal kinase (JNK) in endothelial outgrowth cells (EOCs). Methods The mononuclear cells were harvested from umbilical cord blood by ficoll density gradient centrifugation, and induced into EOCs and then expanded in vitro. The identified EOCs were treated with different concentrations of ADMA (0, 1, 5, 10, 20 μmol/L) for 48 h. The adherent cells were treated with 10 μmol/L ADMA,then different concentrations of JNK specific inhibitor SP600125 (0, 5,10,20 and 40 μmol/L) were added and incubated for 48 hours. Caspase-3 activity was measured by microplate reader. Apoptotic incidences of EOCs were quantitatively determined by flow cytometry. The expression of Caspase- 3 and phosphorylase-JNK (p-JNK) were detected by Western blot assay. Results The treatment of ADMA (1-20 μmol/L) significantly induced apoptosis in EOCs by enhancing Caspase-3 express and also induced phosphorylation of JNK (P<0.05). Meantime, the JNK specific inhibitor SP600125 could attenuate the apoptosis induced by ADMA during this process (F=6.733,P<0.05) and inhibit the expression of Caspase-3 and p-JNK. Conclusion ADMA can induce apoptosis in EOC, which may be achieved by activating JNK signal transduction pathway.
ABSTRACT
The therapeutic effects of endothelial progenitor cells (EPCs) on ischemic stroke have been extensively studied in recent years. However, the differences in early EPCs and endothelial outgrowth cells (EOCs) are still unclear. Clarifications of their respective properties and specific functioning characteristics contribute to better applications of EPCs in ischemic diseases. In this review, we discuss cellular origin, isolation, culture, surface markers of early EPCs and EOCs and relevant applications in neurological diseases. We conclude that EOCs possess all haracteristics of true endothelial progenitors and have potent advantages in EPC-based therapies for ischemic diseases. A number of preclinical and clinical applications of EPCs in neurological diseases are under study. More studies are needed to determine the specific characteristics of EPCs and the relevant mechanisms of EPCs for neurological diseases.