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

• Published in: Acta pharmacologica Sinica Vol. 30; no. 2; pp. 175 - 183
• Main Authors: Yang, Ming-xia, Liu, Zheng-xia, Zhang, Shu, Jing, Yu, Zhang, Shi-jiang, Xie, Wei-ping, Ma, Lei, Zhu, Chang-liang, Wang, Hong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2009; Nature Publishing Group
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Proliferation - drug effects; Cell Shape; Cells, Cultured; Endothelin-1 - metabolism; Humans; Immunology; Internal Medicine; Medical Microbiology; Molecular Sequence Data; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - physiology; Original; original-article; Pharmacology/Toxicology; Propylamines - pharmacology; Pulmonary Artery - cytology; Signal Transduction - physiology; Vaccine; 动脉平滑肌细胞; 细胞增殖; 蛋白质; channel opener; iptakalim; K; proteomics; proliferation; pulmonary arterial smooth muscle cells
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2008.30

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.