Role of Heat Shock Protein 70 in Induction of Stress Fiber Formation in Rat Arterial Endothelial Cells in Response to Stretch Stress

Abstract

We investigated the mechanism by which endothelial cells (ECs) resist various forms of physical stress using an experimental system consisting of rat arterial EC sheets. Formation of actin stress fibers (SFs) and expression of endothelial heat-shock stress proteins (HSPs) in response to mechanical stretch stress were assessed by immunofluorescence microscopy. Stretch stimulation increased expression of HSPs 25 and 70, but not that of HSP 90. Treatment with SB203580, a p38 MAP kinase inhibitor that acts upstream of the HSP 25 activation cascade, or with geldanamycin, an inhibitor of HSP 90, had no effect on the SF formation response to mechanical stretch stress. In contrast, treatment with quercetin, an HSP 70 inhibitor, inhibited both upregulation of endothelial HSP 70 and formation of SFs in response to tensile stress. In addition, treatment of stretched ECs with cytochalasin D, which disrupts SF formation, did not adversely affect stretch-induced upregulation of endothelial HSP 70. Our data suggest that endothelial HSP 70 plays an important role in inducing SF formation in response to tensile stress.

Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial KATPchannel

“…, 2007; Grossini et al. , 2008) and similar to those found to block intracellular pathways associated with the effects of ERK, p38 and Akt in endothelial cells (Luo et al. , 2007; Padmasekar et al.…”

Intracoronary Genistein Acutely Increases Coronary Blood Flow in Anesthetized Pigs through β-Adrenergic Mediated Nitric Oxide Release and Estrogenic Receptors

“…The administration of genistein at a concentration that in the present study induced the highest effects and similar to the one used in pigs and that was able to induce a late but sustained activation of the eNOS in human endothelial cells (51) acutely increased the NO production and level of phosphorylation of eNOS, ERK, p38, and Akt, which are involved in the intracellular signaling of NO production through ␤-adrenoceptors also in PAE cells (34,37,52). The effect on NO synthesis was prevented by the concomitant administration of L-NAME, wortmannin, UO126, and SB203580 using doses that are known to block the effect of prolactin in PAE cells (34) and similar to the ones previously used by others to block intracellular pathways related to ERK, p38, and Akt in endothelial cells (53,54). Thus, the results obtained support the hypothesis of the activation of endothelial NO synthesis being linked to the vasodilation caused by genistein in the anesthetized pig and are in agreement with previous studies (13,15,16,51).…”

Chronic allograft dysfunction: A model disorder of innate immunity

“…[187,188] In addition, as shown in an experimental system consisting of rat arterial endothelial sheets exposed to tensile stretch stress, the expression of the endothelial DAMP, HSP70, was markedly up-regulated. [189] In other lines of studies, the DAMP, HMGB1, was found to play a role in the pathogenesis of hypertension. [190,191] On the other hand, hypertension/mechanical stress-induced PRRs such as TLR2, TLR4, and RAGE, known to recognize mechanical stress-induced DAMPs, have also been demonstrated to be involved in atherogenesis [ Figure 4].…”