Hypoxia decreases K_V1.5 expression by 15-LO/15-HETE in rat / 中国药理学通报

Aim To test the contribution of 15-HETE on expression of KV1.5 channel under hypoxia condition,using CDC or NDGA to block 15-LO/15-HETE,and to observe the effect of hypoxia on KV1.5 channel protein,mRNA expressions in cultured rat pulmonary arterial smooth muscle cells(PASMCs)and pulmonary arterials(PAs).Methods Western blot,RT-PCR and 15-LO blockers,cinnamyl 3,4-dihydroxy-[alpha]-cyanocinnamate(CDC)or nordihydroguiairetic acid(NDGA)were used to identify the role of endogenous 15-HETE on expression of KV1.5 channel in cultured rat pulmonary arterial smooth muscle cells(PASMCs)and PAs.Results(1)The expressions of KV1.5 channel protein and mRNA in PASMCs and PAs preteated with CDC or NDGA greatly increased than those of PASMCs under hypoxia group.(2)Exogenous 15-HETE added to PASMCs pretreated with CDC or NDGA greatly decreased the expression of KV1.5 than that of adding PASMCs pretreated with CDC or NDGA under hypoxia condition.Conclusion The down-regulation of KV1.5 channel expression caused by hypoxia is through endogenous 15-HETE.

Staurosporine aglycone at high concentration causes ERK1/2 phosphorylation in rat pulmonary artery smooth muscle cells / 中国药理学通报

Aim To investigate the effect of SA on induction of ERK1/2 activity in rat pulmonary smooth muscle cells(PASMCs).Methods Western blot analysis was employed to identify the activation of ERK1/2 stimulated by SA at different time points and concentrations in cultured rat PASMCs.Results An unexpected observation showed that ERK1/2 phosphorylation was seen after treatment of SA for 2h at a high concentration(30 ?mol?L-1) but not at lower concentration(from 1 nmol?L-1 to 1 ?mol?L-1).Activation of ERK1/2 pathway could be inhibited by an ERK1/2 inhibitor PD98059 or a protein kinase A(PKA) activator isoproterenol.Conclusion Together,these results suggest that SA has a strong dual regulating effect upon ERK1/2 through PKC and/or PKA pathways in rat PASMCs.