SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Jia, Yong; Gao, Peng; Chen, HouZao; Wan, Yong; Zhang, Ran; Zhang, Zhu-Qin; Yang, Ruifeng; Wang, Xu; Xu, Jing; Liu, Depei

doi:10.1007/s11427-012-4407-7

Cited by 19 publications

(12 citation statements)

References 24 publications

(33 reference statements)

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“…Sirt1 significantly decreased in human endothelial cells after hydrogen peroxide (H 2 O 2 ) exposure [39]. Sirt1 also reduced the ionomycin-induced ICAM-1 expression and attenuated the downregulation of thrombomodulin after particulate matter treatment [40], [41]. As expected, our results showed that inhibition of Sirt1 was associated with the decreased BBB permeability in our co-cultures with or without OGD exposure.…”

Section: Discussionsupporting

confidence: 81%

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

et al. 2018

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Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are two well-characterized members of the silent information regulator 2 (Sir2) family of proteins. Both Sirt1 and Sirt3 have been shown to play vital roles in resistance to cellular stress, but the interaction between these two sirtuins has not been fully determined. In this study, we investigated the role of Sirt1-Sirt3 axis in blood-brain barrier (BBB) permeability after ischemia in vitro. Human brain microvascular endothelial cells and astrocytes were co-cultured to model the BBB in vitro and oxygen and glucose deprivation (OGD) was performed to mimic ischemia. The results of transepithelial electrical resistance (TEER) showed that suppression of Sirt1 via siRNA or salermide significantly decreased BBB permeability, whereas Sirt3 knockdown increased BBB permeability. In addition, Sirt1 was shown to regulate Sirt3 expression after OGD through inhibiting the AMPK-PGC1 pathway. Application of the AMPK inhibitor compound C partially prevented the effects of Sirt1-Sirt3 axis on BBB permeability after OGD. The results of flow cytometry and cytochrome c release demonstrated that Sirt1 and Sirt3 exert opposite effects on OGD-induced apoptosis. Furthermore, suppression of Sirt1 was shown to attenuate mitochondrial reactive oxygen species (ROS) generation, which contribute to the Sirt1-Sirt3 axis-induced regulation of BBB permeability and cell damage. In summary, these findings demonstrate that the Sirt1-Sirt3 axis might act as an important modulator in BBB physiology, and could be a therapeutic target for ischemic stroke via regulating mitochondrial ROS generation.

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Section: Discussionsupporting

confidence: 81%

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

et al. 2018

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“…It was reported that Sirt1 reduces endothelial activation 42 , and overexpression of Sirt1 in ECs inhibits atherosclerosis 33 . Mechanistically, adenovirus-mediated over-expression of Sirt1 significantly inhibits PMA/Ionomycin-induced ICAM-1 expression in human umbilical vein ECs, whereas knockdown of Sirt1 by RNA interference (RNAi) results in increased expression of ICAM-1 and increases NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays in HUVECs 43 . However, the issue of whether caspase-1 in aortic ECs senses hyperlipidemia to initiate vascular inflammation via inhibiting Sirt1 was not examined until this report.…”

Section: Discussionmentioning

confidence: 99%

Early Hyperlipidemia Promotes Endothelial Activation via a Caspase-1-Sirtuin 1 Pathway

Yin

Sha

et al. 2015

ATVB

170

223

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Objective The role of receptors for endogenous metabolic danger signals-associated molecular patterns (DAMPs) has been characterized recently as bridging innate immune sensory systems for DAMPs to initiation of inflammation in bone marrow-derived cells such as macrophages. However, it remains unknown whether endothelial cells (ECs), the cell type with the largest numbers and the first vessel cell type exposed to circulating DAMPs in the blood, can sense hyperlipidemia. This report determined whether caspase-1 plays a role in ECs in sensing hyperlipidemia and promoting EC activation. Approach and Results Using biochemical, immunological, pathological and bone marrow transplantation methods together with the generation of new apoplipoprotein E (ApoE)−/−/caspase-1−/− double knock-out mice we made the following observations: 1) early hyperlipidemia induced caspase-1 activation in ApoE−/− mouse aorta; 2) caspase-1−/−/ApoE−/− mice attenuated early atherosclerosis; 3) caspase-1−/−/ApoE−/− mice had decreased aortic expression of pro-inflammatory cytokines and attenuated aortic monocyte recruitment; and 4) caspase-1−/−/ApoE−/− mice had decreased EC activation including reduced adhesion molecule expression and cytokine secretion. Mechanistically, oxidized lipids activated caspase-1 and promoted pyroptosis in ECs by a ROS mechanism. Caspase-1 inhibition resulted in accumulation of sirtuin 1 (Sirt1) in the ApoE−/− aorta, and Sirt1 inhibited caspase-1 upregulated genes via activator protein-1 (AP-1) pathway. Conclusions Our results demonstrate for the first time that early hyperlipidemia promotes EC activation before monocyte recruitment via a caspase-1-Sirt1-AP-1 pathway, which provides an important insight into the development of novel therapeutics for blocking caspase-1 activation as early intervention of metabolic cardiovascular diseases and inflammations.

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“…We found that SIRT1 inhibited PMA/Io-induced NF-κB [33] and NFAT transcriptional activity. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT or NF-κB activation.…”

Section: Discussionmentioning

confidence: 75%

The Involvement of NFAT Transcriptional Activity Suppression in SIRT1-Mediated Inhibition of COX-2 Expression Induced by PMA/Ionomycin

Jia

Huang

et al. 2014

PLoS ONE

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SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis.

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SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Cited by 19 publications

References 24 publications

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

Early Hyperlipidemia Promotes Endothelial Activation via a Caspase-1-Sirtuin 1 Pathway

The Involvement of NFAT Transcriptional Activity Suppression in SIRT1-Mediated Inhibition of COX-2 Expression Induced by PMA/Ionomycin

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