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

Abstract

Aim:To investigate the anti-proliferative effect of iptakalim (Ipt), a newly selective K ATP 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 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 K ATP 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-X L by opening the K ATP 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.

Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression

“…The expression of NUP54 is increased, which is an essential protein present in a multiprotein complex that is primarily required for nuclear protein import . The abnormal expression of NUP54 could inhibit the proliferation of human pulmonary arterial smooth muscle cells by opening the K ATP channel . In psoriatic T cells, increased expression of NUP54 may influence the cell proliferation by affecting nuclear protein import.…”

“…33 The abnormal expression of NUP54 could inhibit the proliferation of human pulmonary arterial smooth muscle cells by opening the K ATP channel. 34 In psoriatic T cells, increased expression of NUP54 may influence the cell proliferation by affecting nuclear protein import. These genes were not different in MZ-CP.…”

The effects of siRNA against RPL22 on ET-1-induced proliferation of human pulmonary arterial smooth muscle cells

“…Our previous study showed that iptakalim (14,15), inhibited ET-1 synthesis in cultured endothelial cells and suppressed ET-1-induced proliferation of HPASMCs in vitro (17,25). In a proteomic study, it was found that iptakalim significantly inhibited protein expression of RPL22 in HPASMCs (16). Therefore, we presumed that RPL22 may be involved in the proliferation of HPASMCs.…”

“…Moreover, RPL22 deficiency has been reported to selectively arrest development of T cells at the β-selection checkpoint by inducing their death (13). Our preceding research showed that iptakalim, a selective K ATP channel opener (14,15), suppressed ET-1-induced HPASMC proliferation and significantly inhibited RPL22 expression in HPASMCs (16). It was presumed that RPL22 may be involved in the proliferation of HPASMCs.…”

Protein expression by human pulmonary artery smooth muscle cells containing a BMPR2 mutation and the action of ET-1 as determined by proteomic mass spectrometry

“…had reported that 27 proteins were up- or down-regulated by ET-1 and then differentially affected by the selective K ATP channel opener iptakalim in normal human pulmonary arterial smooth muscle cells, but these authors did not provide a list of the proteins that differed between untreated and ET-1 stimulated cells. 6 As shown in Figure 2, Dupont et al . characterized 50 proteins as intracellular proteins expressed in human arterial smooth muscle cells through gel-based protein analysis.…”