Pro-inflammatory Macrophages suppress PPARγ activity in Adipocytes via S-nitrosylation

Yin, Ruiying; Li, Fang; Li, Yingjia; Xue, Peng; Li, Yazi; Guan, Youfei; Chang, Yongsheng; Chen, Chang; Wang, Nanping

doi:10.1016/j.freeradbiomed.2015.10.406

Cited by 35 publications

(31 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, our data do not exclude the possibility that infiltrated immune cells (e.g., macrophages) may contribute to the increased expression of pro-inflammatory genes, such as TNF-α, IL-1β and iNOS. It is important to note that NO produced by iNOS in macrophages may be capable of inducing nitrosative stress in adjacent cells, which is exemplified by adipose tissue inflammation by macrophage iNOS in obesity-induced diabetes [55]. …”

Section: Discussionmentioning

confidence: 99%

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

et al. 2017

View full text Add to dashboard Cite

Inflammation and apoptosis develop in skeletal muscle after major trauma, including burn injury, and play a pivotal role in insulin resistance and muscle wasting. We and others have shown that inducible nitric oxide synthase (iNOS), a major mediator of inflammation, plays an important role in stress (e.g., burn)-induced insulin resistance. However, it remains to be determined how iNOS induces insulin resistance. Moreover, the interrelation between inflammatory response and apoptosis is poorly understood, although they often develop simultaneously. Nuclear factor (NF)-κB and p53 are key regulators of inflammation and apoptosis, respectively. Sirt1 inhibits p65 NF-κB and p53 by deacetylating these transcription factors. Recently, we have shown that iNOS induces S-nitrosylation of Sirt1, which inactivates Sirt1 and thereby increases acetylation and activity of p65 NF-κB and p53 in various cell types, including skeletal muscle cells. Here, we show that iNOS enhances burn-induced inflammatory response and apoptotic change in mouse skeletal muscle along with S-nitrosylation of Sirt1. Burn injury induced robust expression of iNOS in skeletal muscle and gene disruption of iNOS significantly inhibited burn-induced increases in inflammatory gene expression and apoptotic change. In parallel, burn increased Sirt1 S-nitrosylation and acetylation and DNA-binding capacity of p65 NF-κB and p53, all of which were reversed or ameliorated by iNOS deficiency. These results indicate that iNOS functions not only as a downstream effector but also as an upstream enhancer of burn-induced inflammatory response, at least in part, by Sirt1 S-nitrosylation-dependent activation (acetylation) of p65 NF-κB. Our data suggest that Sirt1 S-nitrosylation may play a role in iNOS-mediated enhanced inflammatory response and apoptotic change, which, in turn, contribute to muscle wasting and supposedly to insulin resistance after burn injury.

show abstract

Section: Discussionmentioning

confidence: 99%

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Following incubation with no fat milk at 25˚C for 20 min, the membranes were reacted with anti-phospho-AMPKα antibody (1:1,000) and anti-AMPKα antibody (1:1,000) at 4˚C overnight, then reacted with appropriate horseradish peroxidase-conjugated secondary antibodies (1:3,000) for 2 h at 25˚C. Proteins were visualized with an enhanced chemiluminescence kit, as previously described (16). Densitometry analysis was performed for three independent experiments using the Image J Gel Analysis tool (National Institutes of Health, Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Dipeptidyl peptidase-4 inhibitor sitagliptin prevents high glucose-induced apoptosis via activation of AMP-activated protein kinase in endothelial cells

Wang

et al. 2017

Molecular Medicine Reports

Self Cite

View full text Add to dashboard Cite

Diabetes mellitus (DM), which is a chronic metabolic disorder, is the primary risk factor of life‑threatening vascular complications. Endothelial apoptosis is important in the development of the initial vascular lesion preceding the diabetic disease. Sitagliptin is a dipeptidyl peptidase‑4 (DPP‑4) inhibitor and extensively used in the clinical treatment of DM. DPP‑4 inhibitors have been demonstrated to be beneficial in the improvement of endothelial homeostasis, however the molecular mechanism by which they exhibit these effects remains to be elucidated. The effect of sitagliptin on endothelial apoptosis was examined in cultured human umbilical vein endothelial cells (HUVECs) incubated with high glucose (HG). The present study demonstrated that treatment of HUVECs with HG increased reactive oxygen species (ROS) production, stimulated mitochondrial depolarization and resulted in cell apoptosis. Pretreatment of HUVECs with sitagliptin significantly prevented HG‑induced endothelial apoptosis. It was further demonstrated that sitagliptin effectively inhibited ROS generation and mitochondrial membrane potential collapse. Similarly, adenosine monophosphate‑activated protein kinase (AMPK) activation by sitagliptin protected against HG‑induced ROS production, mitochondrial membrane potential collapse and endothelial cell apoptosis, as detected via western blotting and flow cytometry analysis. The present study therefore revealed a novel mechanism of sitagliptin‑mediated AMPK activation in preventing endothelial apoptosis and indicated the therapeutic potential of sitagliptin in vascular complications associated with endothelial apoptosis.

show abstract

“…Nevertheless, increased total protein S ‐nitrosylation, an alternative sign of ONOO − acting, has been detected in intra‐abdominal adipose tissue of obese humans and high fat‐fed or leptin‐deficient ob/ob mice (Ovadia et al , ). Importantly, Yin et al () recently revealed the role of increased S ‐nitrosylation as the mechanism that links obesity‐associated inflammation, lower PPARγ activity and insulin resistance in adipose tissue. They found that iNOS‐mediated increase of nitro‐oxidative stress translates from macrophages to adipocytes leading to S ‐nitrosylation of PPARγ on Cys 168 .…”

Section: Introductionmentioning

confidence: 99%

“…This in turn potentiates proteasomal degradation of PPARγ, decreasing its transcriptional function. Moreover, expression level of the main PPARγ‐regulated insulin‐sensitizing adipokine, adiponectin, was also lower as a result of increased S ‐nitrosylation of PPARγ (Yin et al , ). Similar results were observed in vivo , in visceral adipose tissue of obese diabetic db/db mice (Yin et al , ).…”

Section: Introductionmentioning

confidence: 99%

Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management

Janković

Korać

Buzadžić

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

show abstract

Pro-inflammatory Macrophages suppress PPARγ activity in Adipocytes via S-nitrosylation

Cited by 35 publications

References 45 publications

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53

Dipeptidyl peptidase-4 inhibitor sitagliptin prevents high glucose-induced apoptosis via activation of AMP-activated protein kinase in endothelial cells

Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management

Contact Info

Product

Resources

About