A novel butyrolactone derivative inhibited smooth muscle cell migration and proliferation and maintained endothelial cell functions through selectively affecting Na, K‐ATPase activity and mitochondria membrane potential during in vitro angiogenesis

Abstract

We have found that 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran -2(3H)-one (3BDO), could effectively suppress human umbilical vascular endothelial cell (HUVEC) apoptosis induced by deprivation of fibroblast growth factor-2 and serum. Here, our purpose was to investigate whether 3BDO could modulate angiogenesis and its possible acting mechanism. The effect of 3BDO on angiogenesis was investigated by capillary-like tubule formation and rat aortic ring assay. Proliferation and migration of cells were detected by counting living cell number and scraping cell monolayer, respectively. Na, K-ATPase activity was measured spectrophotometrically. Mitochondrial membrane potential was analyzed using tetramethylrhodamine methylester fluorescence by confocal microscopy. Our results showed that 3BDO inhibited migration and proliferation of vascular smooth muscle cells (VSMCs), but maintained migration and tubule formation of HUVECs. In HUVECs, 3BDO inhibited Na, K-ATPase activity, but had no effect on mitochondria membrane potential. In VSMCs, it did not affect Na, K-ATPase activity, but depressed mitochondria membrane potential obviously. The data showed that 3BDO had selective effects on HUVECs and VSMCs, it might perform its role through the selective effects on the activity of Na, K-ATPase and the mitochondria membrane potential in HUVECs and VSMCs.

Manganese Induces Oxidative Stress, Redox State Unbalance and Disrupts Membrane Bound ATPases on Murine Neuroblastoma Cells In Vitro: Protective Role of Silymarin

“…Na + -K + -ATPase and Ca 2+ -ATPase were measured as previously described [16, 36]. The inorganic phosphate–molybdate complex was quantitated by spectrophotometer at 690 nm.…”

“…In mitochondrial preparations, N-acetylcysteine (NAC), glutathione, and vitamin C prevent ROS production caused by high concentrations of Mn [16]. In cultured astrocytes, Chen and Liao [17] observe that NAC attenuates the pro-oxidant effects of Mn.…”

The roles of integrin β4 in Vascular Endothelial Cells

“…SFO, even in the presence of serum and FGF‐2, can inhibit endothelial angiogenesis through inducing apoptosis (Zhao et al, 2006). In contrast, 3BDO, which inhibits apoptosis of HUVECs, facilitates endothelial migration and tubule formation through inhibiting Na, K‐ATPase activity (Meng et al, 2008). In addition, chloroquine (CQ) can induce HUVEC vacuolation and accumulation of microtubule‐associated protein 1 light chain 3‐II (MAP1 LC3‐II), a specific marker for autophagy.…”

An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E-/- mice

“…Further study indicated that 3BDO selectively protected vascular ECs (VECs) and inhibited vascular smooth muscle cell (VSMC) proliferation and migration18. Moreover, 3BDO could inhibit the injury induced by chloroquine and lipopolysaccharide in HUVECs1920.…”