SIRT3 diminishes inflammation and mitigates endotoxin-induced acute lung injury

Kurundkar, Deepali; Kurundkar, Ashish; Bone, Nathaniel B.; Becker, Eugene; Liu, Wanqu; Chacko, Balu K.; Darley‐Usmar, Victor; Żmijewski, Jaroslaw W.; Thannickal, Victor J.

doi:10.1172/jci.insight.120722

Cited by 123 publications

(94 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 41 A SIRT3 activator compound also failed to demonstrate a protective role in SIRT3- knockout mice with acute lung injury. 12 …”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have indicated that SIRT3 activation has antioxidative and anti-inflammatory effects. 11 , 12 In this study, we therefore used the SIRT3-activating compound honokiol (HKL) to explore the role of SIRT3 in radioprotection. HKL, also known as 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, is a phenolic compound isolated from Magnolia grandiflora that has various properties, 13 including neuroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

et al. 2020

View full text Add to dashboard Cite

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

show abstract

“… 41 A SIRT3 activator compound also failed to demonstrate a protective role in SIRT3- knockout mice with acute lung injury. 12 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Boniakowski, et al showed that under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation, indicating that SIRT3 is essential for controlling inflammation in diabetic wounds. Another study reported that SIRT3 could diminish inflammation and mitigated endotoxin‐induced acute lung injury (ALI), suggesting that the induction/activation of SIRT3 may serve as a new therapeutic strategy in ALI. Besides, SIRT3 deficiency aggravated cisplatin‐induced nephrotoxicity mainly by increasing renal inflammation .…”

Section: Discussionmentioning

confidence: 99%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

show abstract

“…Another study shows that HMGB1 induces NLRP3 activation via NF-κB [69]. Recent studies suggested that reduction of the Sirt3 expression induced the activation of HMGB1, NF-κB, NLRP3, and caspase-1 and upregulation of the Sirt3 expression inhibited the activation of NF-κB, HMGB1, NLRP3, and caspase-1 [52,70,71]. In the present study, our results revealed that MSCs effectively reduced the expression levels of p-NF-κB p65/NF-κB p65, HMGB1, RAGE, NLPRP3, and cleaved caspase-1 and then significantly inhibited the levels of IL-1β, TNF-α, ICAM-1, and MMP9.…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats

Yang

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Diabetes affects a variety of organs such as the kidneys, eyes, and liver, and there is increasing evidence that the lung is also one of the target organs of diabetes and imbalance of Sirt3-mediated stress responses such as inflammation, oxidative stress, apoptosis, autophagy, and ER stress may contribute to diabetic lung fibrosis. Although previous studies have reported that mesenchymal stem cells (MSCs) have beneficial effects on various diabetic complications, the effect and mechanisms of MSCs on diabetes-induced lung injury are not clear. In this study, the STZ-induced diabetes model was constructed in rats, and the effect and potential mechanisms of bone marrow MSCs on diabetic lung fibrosis were investigated. The results revealed that fibrotic changes in the lung were successfully induced in the diabetic rats, while MSCs significantly inhibited or even reversed the changes. Specifically, MSCs upregulated the expression levels of Sirt3 and SOD2 and then activated the Nrf2/ARE signaling pathway, thereby controlling MDA, GSH content, and iNOS and NADPH oxidase subunit p22phox expression levels in the lung tissue. Meanwhile, high levels of Sirt3 and SOD2 induced by MSCs reduced the expression levels of IL-1β, TNF-α, ICAM-1, and MMP9 by suppressing the NF-κB/HMGB1/NLRP3/caspase-1 signaling pathway, as well as regulating the expression levels of cleaved caspasese-3, Bax, and Bcl2 by upregulating the expression level of P-Akt, thereby inhibiting the apoptosis of the lung tissue. In addition, MSCs also regulated the expression levels of LC3, P62, BiP, Chop, and PERK, thereby enhancing autophagy and attenuating endoplasmic reticulum stress. Taken together, our results suggest that MSCs effectively attenuate diabetic lung fibrosis via adjusting Sirt3-mediated responses, including inflammation, oxidative stress, apoptosis, autophagy, and endoplasmic reticulum stress, providing a theoretical foundation for further exploration of MSC-based diabetic therapeutics.

show abstract

SIRT3 diminishes inflammation and mitigates endotoxin-induced acute lung injury

Cited by 123 publications

References 53 publications

Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats

Contact Info

Product

Resources

About