| Autor: |
Liu Y; Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China, 130033., Chen F; Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China, 130033., Ji L; Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China, 130033., Zhang L; Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China, 130033., Xu YJ; Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Center, and Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada., Dhalla NS; Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Center, and Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada. |
| Abstrakt: |
Lysophosphatidic acid (LPA) is an important lipid molecule for signal transduction in cell proliferation. Although the effects of LPA on vascular smooth muscle (VSM) cell growth have been reported previously, the underlying mechanisms of its action are not fully understood. The present study was undertaken to investigate the effects of some inhibitors of different protein kinases and other molecular targets on LPA-induced DNA synthesis as well as gene expression in the aortic VSM cells. The DNA synthesis was studied by the [ 3 H]thymidine incorporation method and the gene expression was investigated by the real-time PCR technique. It was observed that the LPA-induced DNA synthesis was attenuated by inhibitors of protein kinase C (PKC) (staurosporine, calphostin C, and bisindolylmaleimide), phosphoinositide 3-kinase (PI3K) (wortmannin and LY294002), and ribosomal p 70S6 kinase ( p 70S6K) (rapamycin). The inhibitors of guanine protein coupled receptors (GPCR) (pertussis toxin), phospholipase C (PLC) (U73122 and D609), and sodium-hydrogen exchanger (NHE) (amiloride and dimethyl amiloride) were also shown to depress the LPA-induced DNA synthesis. Furthermore, gene expressions for PLC β1 isoform, PKC δ and ε isoforms, casein kinase II β isoform, and endothelin-1A receptors were elevated by LPA. These results suggest that the LPA-induced proliferation of VSM cells is mediated through the activation of GPCR and multiple protein kinases as well as gene expressions of some of their specific isoforms. |
