Mechanism of PKC activity affecting the adhesion reaction of endothelial cells with monocytes

Li, Lihua; Xu, Suining; Yan, Jinchuan; Li, Yuefeng; Wang, Xiaodong; Du, Rui; Zhu, Jie; Fu, Xianli; Xu, Xiao; Wang, Zhongqun

doi:10.1016/j.ijcard.2014.12.136

Cited by 5 publications

(7 citation statements)

References 8 publications

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“…PKC is an important signal transduction molecule in cells. Currently PKC are divided into 3 subtypes, traditional PKC (α, βI, βII, γ), novel PKC (δ, ε, η, θ), atypical PKC (ζ, λ ) [8]. Several studies have shown that cPKCβII plays very important role in the development of atherosclerosis, and its activation is the process of membrane translocation, that is, cPKCβII translocates from the cytoplasm to the cell membrane [20].…”

Section: Discussionmentioning

confidence: 99%

“…We further found that uremia accelerated the progression of atherosclerosis in ApoE −/− mice and exogenous H 2 S can inhibit the progression of atherosclerosis in uremia ApoE −/− mice. Protein kinase C (PKC) is an important signal transduction molecule in cells [8]. Akt is one of the most versatile kinases in the human kinome and is critical regulator of human physiology that controls diverse cellular functions [9].…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

Xiong

Song

et al. 2019

BMC Nephrol

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Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial. Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta. Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group). Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

Xiong

Song

et al. 2019

BMC Nephrol

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“…Further studies will be necessary to demonstrate the effect of the overexpression of mTOR/ mTORC2 on adhesion molecule expression and the number of macrophages adhering to HUVECs. Other studies have also shown that PKC regulates cell adhesion; enzymatically modified LDL (E-LDL) induced endothelial cell adhesion, promoted the transposition and activation of PKC, inhibited the expression of IκBα, and enhanced the expression of ICAM-1 [41] . We also noted that the inhibition of mTOR by rapamycin or the downregulation of rictor decreased the phosphorylation of PKC ( Figure 4B and C).…”

Section: Discussionmentioning

confidence: 99%

Rapamycin inhibits ox-LDL-induced inflammation in human endothelial cells in vitro by inhibiting the mTORC2/PKC/c-Fos pathway

et al. 2017

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Rapamycin and its derivative possess anti-atherosclerosis activity, but its effects on adhesion molecule expression and macrophage adhesion to endothelial cells during atherosclerosis remain unclear. In this study we explored the effects of rapamycin on ox-LDL-induced adhesion molecule expression and macrophage adhesion to endothelial cells in vitro and the underlying mechanisms. Ox-LDL (6-48 μg/mL) dose-dependently increased the protein levels of two adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and E-selectin, in human umbilical vein endothelial cells (HUVECs), whereas pretreatment with rapamycin (1-10 μmol/L) dose-dependently inhibited ox-LDL-induced increase in the adhesion molecule expression and macrophage adhesion to endothelial cells. Knockdown of mTOR or rictor, rather than raptor, mimicked the effects of rapamycin. Ox-LDL (100 μg/mL) time-dependently increased PKC phosphorylation in HUVECs, which was abolished by rapamycin or rictor siRNA. Pretreatment with PKC inhibitor staurosporine significantly reduced ox-LDL-stimulated adhesion molecule expression and macrophage adhesion to endothelial cells, whereas pretreatment with PKC activator PMA/TPA attenuated the inhibitory effect of rapamycin on adhesion molecule expression. Ox-LDL (100 μg/mL) time-dependently increased c-Fos levels in HUVECs, and pretreatment with rapamycin or rictor siRNA significantly decreased expression of c-Fos. Knockdown of c-Fos antagonized ox-LDL-induced adhesion molecule expression and macrophage adhesion to endothelial cells. Our results demonstrate that rapamycin reduces ox-LDL-stimulated adhesion molecule expression and macrophage adhesion to endothelial cells by inhibiting mTORC2, but not mTORC1, and mTORC2 acts through the PKC/c-Fos signaling pathway.

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“…There is convincing evidence demonstrating that PKC activation is involved in endothelial dysfunction and monocytes adhesion to ECs [ 16 ]. Furthermore, the activation of NF-κB is a necessary downstream event of enhanced monocyte adhesion [ 16 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion

et al. 2017

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Several studies have reported a strong association between high plasma level of trimethylamine N-oxide (TMAO) and atherosclerosis development. However, the exact mechanism underlying this correlation is unknown. In the present study, we try to explore the impact of TMAO on endothelial dysfunction. After TMAO treatment, human umbilical vein endothelial cells (HUVECs) showed significant impairment in cellular proliferation and HUVECs-extracellular matrix (ECM) adhesion compared with control. Likewise, TMAO markedly suppressed HUVECs migration in transwell migration assay and wound healing assay. In addition, we found TMAO up-regulated vascular cell adhesion molecule-1 (VCAM-1) expression, promoted monocyte adherence, activated protein kinase C (PKC) and p-NF-κB. Interestingly, TMAO-stimulated VCAM-1 expression and monocyte adherence were diminished by PKC inhibitor. These results demonstrate that TMAO promotes early pathological process of atherosclerosis by accelerating endothelial dysfunction, including decreasing endothelial self-repair and increasing monocyte adhesion. Furthermore, TMAO-induced monocyte adhesion is partly attributable to activation of PKC/NF-κB/VCAM-1.

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Mechanism of PKC activity affecting the adhesion reaction of endothelial cells with monocytes

Cited by 5 publications

References 8 publications

Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

Rapamycin inhibits ox-LDL-induced inflammation in human endothelial cells in vitro by inhibiting the mTORC2/PKC/c-Fos pathway

Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion

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