Short-chain fatty acid butyrate acid attenuates atherosclerotic plaque formation in apolipoprotein E-knockout mice and the underlying mechanism / 生理学报

This study was designed to evaluate the role of short-chain fatty acid butyrate acid on intestinal morphology and function, and atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE

AMP-activated protein kinase activation regulates adhesion of monocytes to vascular endothelial cells and the underlying mechanism / 生理学报

The present study was aimed to explore the effect of AMP-activated protein kinase (AMPK) on monocyte adhesion to vascular endothelial cells and underlying molecular mechanism. Tumor necrosis factor α (TNFα)-activated human aortic endothelial cells (HAECs) were treated with different concentrations of AMPK agonist 5-Aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR) or AMPK inhibitor compound C. And other HAECs were overexpressed with constitutive active or dominant negative AMPK protein and then treated with TNFα. The rates of monocytes adhering to endothelial cells were detected by fluorescent staining. Intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA levels and protein secretions were detected by quantitative PCR and ELISA, respectively. Acetylation of NF-κB p65 at lysine 221 site was assessed by Western blot. NF-κB p65 DNA binding activity was analyzed by an ELISA-based method. By using small interfering RNA based strategy, p300 expression in HAECs was down-regulated and then cells were incubated with TNFα. NF-κB p65 DNA binding activity, ICAM-1 and VCAM-1 expressions and adhesion rates were detected, respectively. The activity of p300 was also detected by ELISA. The results showed that AICAR treatment significantly reduced monocyte-endothelial adhesion rate, as well as ICAM-1 and VCAM-1 mRNA levels and protein secretions, in TNFα-activated HAECs. Moreover, transfection of constitutive active AMPKα but not dominant negative AMPKα strongly diminished TNFα-induced upregulation of ICAM-1 and VCAM-1 mRNA expressions and secretions, as well as monocyte-endothelial adhesion. Furthermore, AMPK activation decreased TNFα-mediated acetylation of NF-κB p65 at Lys221 site and reduced NF-κB p65 DNA binding activity. Silencing p300 by siRNA significantly abolished the effect of TNFα- induced adhesion molecules expression and monocyte-endothelial adhesion. Blocking AMPK activation by compound C almost completely reversed the effect of AICAR exerted on HAECs. These results suggest AMPK activation suppresses monocyte-endothelial adhesion, and the underlying mechanism is relevant to the inhibition of p300 activity and NF-κB p65 transcriptional activity.

Effects of CGRP on the E-cadherin expression in human bronchial epithelial cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To discuss the effect of calcitonin gene-related peptides (CGRP) on epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs) in vitro.</p><p><b>METHODS</b>The effect of CGRP on E-cd protein and mRNA expression in both normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR. The signal transduction pathways of CGRP were observed by using protein kinase C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).</p><p><b>RESULTS</b>CGRP increased E-cd mRNA and protein expressions of normal and O3-challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of CGRP on E-cd expression was partly abolished.</p><p><b>CONCLUSION</b>CGRP increased in cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose-dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC and CaM pathways.</p>

Effects of CGRP on LPS-induced MMP-9 secretion by alveolar macrophages / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of calcitonin-gene-related peptide (CGRP) on LPS-induced MMP-9 secretion by alveolar macrophages (AM) in vitro.</p><p><b>METHODS</b>The supernatant of LPS-induced Wistar rat AM from different intervention groups were collected to measure the activity by gelatin zymography.</p><p><b>RESULTS</b>(Only secreting a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in a concentration-dependent manner (p < 0.01). (2) The activity of MMP-9 in CGRP intervention groups at different levels were significantly lower than those in non-intervention group (p < 0.01). (3) The inhibiting effects of CGRP were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (p < 0.05).</p><p><b>CONCLUSION</b>These data suggested that CGRP involved in the MMP-9 secretion by AM, partly, via PKC and CaM pathway.</p>

Effects of vasoactive intestinal peptide on LPS-induced MMP-9 expression by alveolar macrophages in rats / 中南大学学报(医学版)

OBJECTIVE@#To explore the role of vasoactive intestinal peptide (VIP) on LPS-induced MMP-9 expression by alveolar macrophages (AM) in rats.@*METHODS@#LPS-induced cultured Wistar rats AMs were treated with different concentrations of VIP (10(-10) to approximately 10(-6) mol/L) for 24 h. AMs and the supernatant were collected to measure the MMP-9 expression and activity by RT-PCR and gelatin zymography, respectively. Results The MMP-9 activity and expression of LPS-induced AMs were significantly higher than those in the control group (P < 0.01). VIP (10(-9) to approximately 10(-6) mol/L) down-regulated LPS-induced MMP-9 activity and its expression. The effects were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (P < 0.01).@*CONCLUSION@#VIP can decrease LPS-induced MMP-9 activity and its expression, which may be related to protein kinase C and calmodulin pathway. VIP may have protective roles in the lung injury.