Propofol attenuates monocyte-endothelial adhesion via modulating connexin43 expression in monocytes

Ji, Haocong; Qiu, Rongzong; Gao, Xin; Zhang, Rui; Li, Xianlong; Hei, Ziqing; Yuan, Ding

doi:10.1016/j.lfs.2019.116624

Cited by 16 publications

(22 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The important finding in the present study is that alternation of Cx43 expression on HUVECs modulated the activation of MAPKs, manifested as the changes of p-ERK1/2, p-p38, and p-JNK1/2. The carboxyl-terminal domain of Cx43 could interact with some special elements of cellular signaling pathways, such as Src, PKC, and PKA, which provides the possibility that changes of Cx43 expression affect other signaling pathways [2,8,29]. Although inhibiting Cx43 expression on HUVECs could effectively attenuate the activation of ERK1/2, p38, and JNK1/2, it did not mean that all the three signaling pathways could affect related adhesion molecule expression and cell adhesion.…”

Section: Mediators Of Inflammationmentioning

confidence: 99%

“…U0126 was used to inhibit p-ERK1/2 (10 μM, 24 hours, Sigma-Aldrich); SB202190 was used to inhibit p-p38 (10 μM, 24 hours, Sigma-Aldrich); SP600125 was used to inhibit p-JNK1/2 (10 μM, 24 hours, Sigma-Aldrich). [2]. U937 monocytes are labeled with 5 μmol/l calcein-acetoxymethyl ester (Invitrogen) and cultured in the incubator for 30 min.…”

Section: Cell Treatments Dexmedetomidine Is Purchased Frommentioning

confidence: 99%

“…Endothelial dysfunction contributes to the development of both acute inflammatory disease states, such as sepsis and endotoxemia, and chronic inflammatory disease states, such as atherosclerosis, rheumatoid arthritis, diabetes, and inflammatory bowel disease [1,2]. In response to inflammatory stimuli, the vascular endothelium expresses a series of adhesion molecules that play key roles in the recruitment of monocytes to sites of inflammation [3].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells

Chai

Liu

et al. 2020

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

Current studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating monocyte-endothelial adherence. U937 monocytes and human umbilical vein endothelial cells (HUVECs) were used to explore monocyte-endothelial adherence. Two special siRNAs were designed to knock down Cx43 expression on HUVECs. U937-HUVEC adhesion, adhesion-related molecules, and the activation of the MAPK (p-ERK1/2, p-p38, and p-JNK1/2) signaling pathway were detected. Dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), was given as pretreatments to HUVECs. Its effects on Cx43 and U937-HUVEC adhesion were also investigated. The results show that inhibiting Cx43 on HUVECs could attenuate the contents of MCP-1, soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and the nonprocessed variants of the adhesion molecules ICAM-1 and VCAM-1 and ultimately result in U937-HUVEC adhesion decrease. Meanwhile, the activation of MAPKs was also inhibited. U0126 (inhibiting p-ERK1/2) and SB202190 (inhibiting p38) decreased the contents of MCP-1, sICAM-1, and sVCAM-1, but SP600125 (inhibiting p-JNK1/2) had none of these effects. ICAM-1 and VCAM-1 could be regulated in a similar way. Dexmedetomidine pretreatment inhibited Cx43 on HUVECs, the activation of MAPKs, and U937-HUVEC adhesion. Therefore, we conclude that dexmedetomidine attenuates U937-HUVEC adhesion via inhibiting Cx43 on HUVECs modulating the activation of MAPK signaling pathways.

show abstract

Section: Mediators Of Inflammationmentioning

confidence: 99%

Section: Cell Treatments Dexmedetomidine Is Purchased Frommentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells

Chai

Liu

et al. 2020

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Connexins are expressed in almost all human organs and tissues. Cx37, Cx40, and Cx43 are predominantly expressed in cardiovascular system [ 9 , 10 ]. Multiple reports clarify the importance of Cx43 on monocyte-endothelial adherence [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…This kind of interaction provides the possibility that Cx43 expression on cell membrane influences other signaling pathways in cytoplasm. The cross talk between Cx43 and PKC is the basis of Cx43 regulating downstream signaling pathways in cytoplasm [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes

Chai

Cao

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

Ye,

Wang,

Little

et al. 2024

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Propofol attenuates monocyte-endothelial adhesion via modulating connexin43 expression in monocytes

Cited by 16 publications

References 41 publications

Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells

Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells

Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes

Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

Contact Info

Product

Resources

About