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Over-expression of the cellular repressor of E1A-stimulated genes inhibits the apoptosis of human vascular smooth muscle cells in vitro / 生理学报
Acta Physiologica Sinica ; (6): 324-330, 2006.
Article in Chinese | WPRIM | ID: wpr-265448
ABSTRACT
To investigate the effects and molecular mechanisms of the cellular repressor of E1A-stimulated genes (CREG) on the apoptosis of vascular smooth muscle cells (VSMCs), the human internal thoracic artery-Shenyang (HITASY) cells were infected with sense-CREG [pLNCX(2)(+)/CREG] and antisense-CREG [pLXSN(-)/CREG] retrovirus respectively. The stably infected cells were obtained by screening the G418-resistant clones. DAPI nuclei staining and Annexin V/PI FASC assay indicated that over-expression of CREG in HITASY cells infected with pLNCX(2) (+)/CREG inhibited VSMC apoptosis induced by serum deprivation, accompanied with decreased expression of caspase-9 mRNA detected by RT-PCR. Furthermore, Western blot analysis showed that p38 mitogen activated protein kinase (p38 MAPK) expression and activation were significantly enhanced in HITASY cells infected with pLNCX(2) (+)/CREG. The inhibition of CREG protein expression in cells infected with pLXSN(-)/CREG promoted the VSMC spontaneous apoptosis, as well as down-regulated p38 MAPK expression and activation, when cells were cultured with 10% fetal bovine serum (FBS) mediums. These results implicate that the CREG protein has the ability to regulate VSMC apoptosis in which the activation of p38 MAPK is possibly involved. To further identify the role of p38 MAPK in VSMC apoptosis, SB203580, a specific inhibitor of p38 MAPK, was used to inhibit p38 MAPK activity. When p38 MAPK signaling pathway was blocked, the effects that over-expression of CREG protein inhibited VSMC apoptosis disappeared. Taken together, the present work indicates that over-expression of CREG protein inhibits VSMC apoptosis, and this inhibitory effect is partly mediated by p38 MAPK signaling pathway.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Physiology / Repressor Proteins / Signal Transduction / Cells, Cultured / Apoptosis / Cell Biology / Myocytes, Smooth Muscle / P38 Mitogen-Activated Protein Kinases / Caspase 9 / Genetics Type of study: Prognostic study Limits: Humans Language: Chinese Journal: Acta Physiologica Sinica Year: 2006 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Physiology / Repressor Proteins / Signal Transduction / Cells, Cultured / Apoptosis / Cell Biology / Myocytes, Smooth Muscle / P38 Mitogen-Activated Protein Kinases / Caspase 9 / Genetics Type of study: Prognostic study Limits: Humans Language: Chinese Journal: Acta Physiologica Sinica Year: 2006 Type: Article