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Rho kinase mediates Porphyromonas gingivalis outer membrane vesicle-induced suppression of endothelial nitric oxide synthase through ERK1/2 and p38 MAPK.

Abstract：

OBJECTIVE:To investigate the effect of Rho kinase (ROCK) on Porphyromonas gingivalis outer membrane vesicles (OMVs)-induced suppression of endothelial nitric oxide synthase (eNOS) and explore the potential mechanism. DESIGN:Firstly, we investigated the effect of OMVs on total eNOS expression and eNOS activity in Human Umbilical Vein Endothelial Cells (HUVECs) and if ROCK activation is involved. Furthermore, we estimated the effect of ROCK in regulating eNOS expression and the possible underlying mechanism in vitro. At last we confirmed the results by immunohisochemisty for eNOS expression in mouse aorta endothelium exposed to OMVs and inhibitors. RESULTS:We found that OMVs suppressed eNOS expression both at RNA and protein levels in a time- and dose-dependent manner. ROCK activity was observed in this process by detecting phosphorylation of myosin light chain (MLC) and myosin-associated phosphatase type 1 (MYPT-1), which lead to reduced eNOS expression. The suppression of eNOS was significantly reversed by ROCK inhibitor Y-27632. Moreover, Y-27632 pretreatment obviously inhibited the activation of ERK1/2 and p38 MAPKs induced by OMVs, whereas that of JNK was not affected. In addition, blocking ERK1/2 or p38 MAPK by PD98059 and SB203580, respectively attenuated the OMVs-induced eNOS phosphorylation. Ex vivo study shows that OMVs reduced eNOS expression in mouse aorta endothelium. Co-treatment with OMVs and inhibitors could significantly reverse the eNOS suppression. Taken together, these results demonstrate that ROCK mediated OMVs-induced eNOS suppression through ERK1/2 and p38 MAPK. CONCLUSIONS:These data suggest that ROCK may mediate OMVs-induced eNOS expression through ERK1/2 and p38 MAPK.

journal_name

Arch Oral Biol

journal_title

Archives of oral biology

authors

Jia Y,Guo B,Yang W,Zhao Q,Jia W,Wu Y

doi

10.1016/j.archoralbio.2014.12.009

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

488-95

issue

eissn

0003-9969

issn

1879-1506

pii

S0003-9969(14)00321-5

journal_volume

pub_type

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Rho kinase mediates Porphyromonas gingivalis outer membrane vesicle-induced suppression of endothelial nitric oxide synthase through ERK1/2 and p38 MAPK.