Details

Autor(en) / Beteiligte

• Yang, Ming-Xia
• Liu, Zheng-Xia
• Zhang, Shu
• Jing, Yu
• Zhang, Shi-Jiang
• Xie, Wei-Ping
• Ma, Lei
• Zhu, Chang-Liang
• Wang, Hong

Titel

Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth muscle cell proliferation

Ist Teil von

• Acta pharmacologica Sinica, 2009-02, Vol.30 (2), p.175-183

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• Aim： To investigate the anti-proliferative effect of iptakalim （Ipt）, a newly selective KATP channel opener, in endothelin-1（ET-1）-induced human pulmonary arterial smooth muscle cells （PASMCs） using proteomic analysis. Methods： Human PASMCs were incubated with ET-1 （10^-8mol/L） and ET-1 （10^-8mol/L） plus iptaklim （10^-5mol/L） for 24 h. Analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was employed to display the different protein profiles of whole-cell protein from cultures of control, ET-1 treatment alone, and treatment with ET-1 and iptaklim combined. Real time RT-PCR and Western blot analysis were used to confirm the proteomic analysis. Results： When iptakalim inhibited the proliferative effect of ET-1 in human PASMCs by opening the KATp channels, the expression of different groups of cellular proteins was changed, including cytoskeleton-associated proteins, plasma.membrane proteins and receptors, chaperone proteins, ion transport-associated proteins, and glycolytic and metabolism-associated proteins. We found that iptakalim could inhibit the proliferation of human PASMCs partly by affecting the expression of Hsp60, vimentin, nucleoporin P54（NUP54） and Bcl-XL by opening the KATP channel. Conclusion： The data suggest that a wide range of signaling pathways may be involved in abolishing ET-1-induced proliferation of human PASMCs following iptakalim treatment.