Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cells

Abstract

Female astronauts have been reported to have a higher incidence of post-flight orthostatic intolerance (POI) compared with that of their male counterparts. POI may result from increased permeability of the endothelial cell (EC) layer in the vasculature. The goal of this study has been to determine whether estradiol (E(2)) and dihydrotesterone (DHT) alter human umbilical vein ECs (HUVECs) responses to short term (10 min) hypergravity (1-3 g) mimicking the g force experienced by astronauts during liftoff. E(2) and DHT rapidly (within 5 min) activated MAPK (mitogen-activated protein kinase) in HUVEC at 1 g in a receptor-dependent manner. Liftoff inhibited MAPK phosphorylation, and rapid E(2) and DHT activation of MAPK was blocked. Liftoff simulation or brief (5-90 min) treatment with E(2) or DHT at 1 g had no effect on the expression of the EC tight-junction protein occludin. However, 24-h pre-treatment of HUVECs with E(2) and DHT prior to liftoff simulation significantly increased occludin expression, and hypergravity exposure did not alter this increase. These data provide evidence for a possible protective effect of E(2) and DHT on EC function as indicated by increased occludin; this may help maintain the integrity of EC tight junction and could thus retard or reduce the incidence of POI.

Effect of Hypergravity on Endothelial Cell Function and Gene Expression

“…Very different stimulation modalities have been used (continuous or discontinuous, g forces ranging from 2 to 2,000×g, treatments ranging from minutes to days). This could be the reason for contrasting results sometimes obtained by the authors on ECs (Spisni et al 2003;Versari et al 2007;Sumanasekera et al 2006Sumanasekera et al , 2007. Till now the studies have been conducted in HUVECs, where prolonged hypergravity exposure results in inhibited cell growth, enhanced migration and increased NO synthesis (Spisni et al 2003;Versari et al 2007).…”

Hypergravity induces ATP release and actin reorganization via tyrosine phosphorylation and RhoA activation in bovine endothelial cells

“…The activations of FAK and RhoA were observed shortly after the application of hypergravity, and the latter was declined in 10 min, thereby suggesting that these are the initial signals activated by hypergravity. Previous reports showed the inhibition of MAPK phosphorylation [27] and the activation of cyclooxygenase 2 and prostacyclin synthase [24] after the application of hypergravity for 7.5 min and 24 h, respectively, in HUVECs. The former report also described that the inhibition of MAPK persisted at least for 4 h after returning to 1 G gravity [27], whereas hypergravity-induced FAK phosphorylation declined in 20 min in 1 G (Fig.…”

“…They also showed that hypogravity stimulated endothelial growth, enhanced nitric oxide production, and altered actin distribution [29]. Sumanasekera et al reported that brief hypergravity decreased the barrier function, which was attributed to the inhibition of MAPK phosphorylation, in HUVECs [26,27].…”

The Impact of Altered Gravity and Vibration on Endothelial Cells During a Parabolic Flight

“…There will always be a certain amount of vibrations. In addition, there are before and after each phase of microgravity two phases of hypergravity of 1.8 g. The influence of hypergravity on endothelial cells has been studied before, but with different g-forces (3 g ) and different durations of exposure (10 min and 48 h, respectively) [21,22]. Vibrations, however, have not been intensively investigated.…”