Original Article

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

Authors: Ming-xia Yang, Zheng-xia Liu, Shu Zhang, Yu Jing, Shi-jiang Zhang, Wei-ping Xie, Lei Ma, Chang-liang Zhu, Hong Wang
DOI: 10.1038/aps.2008.30

Abstract

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 (10-8 mol/L) and ET-1 (10-8 mol/L) plus iptaklim (10-5 mol/L) for 24 h. Analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was employed to display the different protein profiles of wholecell protein from cultures of control, ET-1 treatment alone, and treatment with ET-1 and iptaklim combined. Real time RTPCR 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.
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