Antiproliferation activity of a naphthoquinone derivative against vascular smooth muscle cells / 中国药理学通报

Aim: To explore the effect of a synthetic naphthoquinone derivative on the proliferation of rat aortic vascular smooth muscle cells(RAVSMCs) stimulated by platelet-derived growth factor BB (PDGF-BB) and to clarify its mechanism underlying the anti-proliferative effect. Methods: The influence of the synthetic naphthoquinone derivative on cell cycle progression and main signal transduction pathway of cell cycle induced by PDGF-BB were investigated by cell proliferation assay, [3H] thymidine incorporation test, cell cycle process analysis and immunoblotting assay. Results: S phase cell percentage in the cell cycle was reduced, while G0/G1 phase cell percentage was increased by the synthetic naphthoquinone in a dose-dependent (0. 1, 0. 5, 1 μmol · L-1) manner. Moreover, DNA synthesis also decreased. The inhibitory rate of PDGF-BB-induced RAVSMCs proliferation achieved the maximum of 44. 4% after 24 h pre-treatment by the synthetic naphthoquinone derivative at the concentration of 1 μmol · L-1. The phosphorylation of extracellular regulated kinase l/2(ERKl/2), Akt, phospholipase C (PLC) γ1 and PDGF receptor β(PDGFRβ) induced by PDGF-BB was significantly decreased (P < 0. 01) by addtion of 1 μmol · L-1 synthetic naphthoquinone derivative. Conclusions: The synthetic naphthoquinone derivative exhibits anti-proliferation activity against RAVSMCs induced by PDGF-BB via blocking the transformation of G0/G1 phase cell into S-phase cell in the cell cycle. The mechanisms might be related to its down-regulatory effect on phosporalation level of ERK1/2, Akt, PLCγ1 and PDGFRβ.

Role of ROS-TRPM7-ERK1/2 axis in high concentration glucose-mediated proliferation and phenotype switching of rat aortic vascular smooth muscle cells.

This study investigated the change of transient receptor potential cation channel subfamily M member 7 (TRPM7) expression in rat aortic vascular smooth muscle cells (RAoSMCs) treated with a high concentration of d-glucose (HG) and its role in promoting the proliferative phenotype of RAoSMCs. Chronic exposure to HG increased TRPM7 protein expression and TRPM7 whole-cell currents in RAoSMCs. By contrast, RAoSMC exposure to high concentration of l-glucose and mannital exhibited no such effect. Mechanistically, HG treatment elevated TRPM7 expression by increasing oxidative stress. Data also demonstrated that HG significantly promoted RAoSMC proliferation. In addition, as indicated by the changes of the expression of VSMC differentiation marker molecules, phenotype switching of RAoSMCs occurred during exposing to HG. TRPM7 knockdown partially blocked the HG effect on phenotype switching and RAoSMC proliferation. This phenomenon was achieved through inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK signaling pathway. These observations suggest that reactive oxygen species-TRPM7-ERK1/2 axis plays an important role in hyperglycemia-induced development of the proliferative phenotype in RAoSMC.