Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43PKC-αNOX2ROS Signaling Pathway in Monocytes
Joint Authors
Yuan, Dongdong
Chai, Yunfei
Yu, Runying
Liu, Yong
Cao, Zhongming
Lei, Liming
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-22
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Dexmedetomidine is widely used for sedating patients in operation rooms or intensive care units.
Its protective functions against oxidative stress, inflammation reaction, and apoptosis have been widely reported.
In present study, we explored the effects of dexmedetomidine on monocyte-endothelial adherence.
We built lipopolysaccharide- (LPS-) induced monocyte-endothelial adherence models with U937 monocytes and human umbilical vein endothelial cells (HUVECs) and observed the effects of dexmedetomidine on U937-HUVEC adhesion.
Specific siRNA was designed to knock-down Connexin43 (Cx43) expression in U937 monocytes.
Gö6976, GSK2795039, and NAC were used to inhibit PKC-α, NOX2, and ROS, respectively.
Then, we detected whether dexmedetomidine could downregulate Cx43 expression and its downstream PKC-α/NOX2/ROS signaling pathway activation and ultimately result in the decrease of U937-HUVEC adhesion.
The results showed that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), could inhibit adhesion of molecule expression (VLA-4 and LFA-1) and U937-HUVEC adhesion.
Simultaneously, it also attenuated Cx43 expression in U937 monocytes.
With the downregulation of Cx43 expression, the activity of PKC-α and its related NOX2/ROS signaling pathway were reduced.
Inhibiting PKC-α/NOX2/ROS signaling pathway with Gö6976, GSK2795039, and NAC, respectively, VLA-4, LFA-1 expression, and U937-HUVEC adhesion were all decreased.
In summary, we concluded that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), decreased Cx43 expression in U937 monocytes and PKC-α associated with carboxyl-terminal domain of Cx43 protein.
With the downregulation of PKC-α, the NOX2/ROS signaling pathway was inhibited, resulting in the decrease of VLA-4 and LFA-1 expression.
Ultimately, U937-HUVEC adhesion was reduced.
American Psychological Association (APA)
Chai, Yunfei& Cao, Zhongming& Yu, Runying& Liu, Yong& Yuan, Dongdong& Lei, Liming. 2020. Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43PKC-αNOX2ROS Signaling Pathway in Monocytes. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1204077
Modern Language Association (MLA)
Chai, Yunfei…[et al.]. Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43PKC-αNOX2ROS Signaling Pathway in Monocytes. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1204077
American Medical Association (AMA)
Chai, Yunfei& Cao, Zhongming& Yu, Runying& Liu, Yong& Yuan, Dongdong& Lei, Liming. Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43PKC-αNOX2ROS Signaling Pathway in Monocytes. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1204077
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204077