Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

Zhao, Wen‐Yu; Zhang, Lei; Sui, Mingxing; Zhu, Youhua; Zeng, Li

doi:10.1038/srep33201

Cited by 86 publications

(77 citation statements)

References 36 publications

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“…7A, F). This is consistent with a previous study showing that NAC inhibited the expression of NLRP3 protein (53).…”

Section: Discussionsupporting

confidence: 94%

“…ROS are well known activators of NLRP3 inflammasome. It is reported that NAC can block the transcription of NLRP3 and pro-IL-1b by scavenging of cellular ROS (53). Other research also found that mtROS scavengers can significantly inhibit the activation of NLRP3 inflammasome (53).…”

Section: Discussionmentioning

confidence: 98%

“…It is reported that NAC can block the transcription of NLRP3 and pro-IL-1b by scavenging of cellular ROS (53). Other research also found that mtROS scavengers can significantly inhibit the activation of NLRP3 inflammasome (53). A recent study reported that mtROS overproduction is associated with increases in NLRP3/IL-1b expression in the kidneys of patients with DN and in Lepr db /Lepr db mice (54).…”

Section: Discussionmentioning

confidence: 99%

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Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy

Chen

Feng

et al. 2018

FASEB j.

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Tubulointerstitial inflammation plays a critical role in the progression of diabetic nephropathy (DN), and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasomes contribute to renal interstitial inflammation in DN. Decreased expression of optineurin (OPTN) is also associated with the progression of DN. We investigated the role of OPTN in activation of the NLRP3 inflammasome in DN. We initially examined the renal biopsy tissues of 172 patients with type 2 DN and 32 nondiabetic patients with renal hamartoma. Expression of renal OPTN was significantly lower in patients with DN and negatively correlated with urinary levels of IL‐1β and IL‐18. Confocal microscopy analysis of the biopsies indicated no NLRP3 or IL‐1β staining in OPTN‐positive renal tubular epithelial cells (RTECs), indicating a negative correlation of OPTN expression with the activation of NLRP3 inflammasome. In vitro studies of murine RTECs indicated the levels of OPTN mRNA and protein decreased significantly after stimulation by a high glucose (HG) treatment. Relative to RTECs given HG., RTECs overexpressing OPTN showed significantly lower levels of NLRP3 expression, cleavage of caspase‐1 and IL‐1β, and release of IL‐1β and IL‐18. Overexpression of OPTN in the presence of HG significantly increased the costaining of microtubule‐associated protein 1A/1B‐Iight chain 3‐II and translocase of outer mitochondrial membrane 20 in RTECs, suggesting that OPTN enhances mitophagy. In addition, mitochondrial division inhibitor 1 blocked the inhibitory effect of OPTN overexpression on the activation of NLRP3 inflammasome in the presence of HG., indicating that OPTN overexpression inhibited NLRP3 inflammasome activation by enhancement of mitophagy. OPTN gene silencing significantly enhanced production of mitochondrial reactive oxygen species (mtROS) in the presence of HG. Compared with HG+OPTN small interfering RNA (siRNA)‐treated RTECs, HG+OPTN siRNA+MitoTempo‐treated RTECs attenuated NLRP3 inflammasome activation, suggesting that OPTN gene silencing activates the NLRP3 inflammasome by increasing mtROS in HG‐treated RTECs. Taken together, our results demonstrate that OPTN inhibits the activation of NLRP3 inflammasome by enhancing mitophagy.—Chen, K., Feng, L., Hu, W., Chen, J., Wang, X., Wang, L., He, Y. Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy. FASEB J. 33, 4571–4585 (2019). http://www.fasebj.org

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“…7A, F). This is consistent with a previous study showing that NAC inhibited the expression of NLRP3 protein (53).…”

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy

Chen

Feng

et al. 2018

FASEB j.

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“…Various studies have demonstrated that excessive ROS promotes necroptosis in various cell types, whereas inhibiting ROS production reduces necroptosis (13)(14)(15)(16). In addition, previous studies revealed that ROS production is augmented in AKI, and that ROS lead to renal tubular epithelium injury via inflammasome activation, mitochondrion damage and tubular epithelium apoptosis (22)(23)(24)(25). To the best of our knowledge, there are no studies that have investigated the effect of ROS on necroptosis in renal tubular epithelium.…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase inhibitor, diphenyleneiodonium prevents necroptosis in HK-2 cells

Dong

Chen

et al. 2017

Biomedical Reports

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Abstract. The aim of the present study was to investigate the protective effect of the NADPH oxidase inhibitor, diphenyleneiodonium (DPI) against necroptosis in renal tubular epithelial cells. A necroptosis model of HK-2 cells was established using tumor necrosis factor-α, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone and antimycin A (collectively termed TZA), as in our previous research. The necroptosis inhibitor, necrostatin-1 (Nec-1) or the NADPH oxidase inhibitor, DPI were administered to the necroptosis model. Production of reactive oxygen species (ROS) was detected by dichlorodihydrofluorescein diacetate in the different groups, and the manner of cell death was identified by flow cytometry. Western blot analysis was used to determine the levels of phosphorylation of receptor-interacting protein kinase 3 (RIP-3) and mixed lineage kinase domain-like (MLKL), which are essential to necroptosis. The results revealed that TZA increased the percentages of propidium iodide-positive HK-2 cells from 1.22±0.69 to 8.98±0.73% (P<0.001), and augmented the phosphorylation of RIP-3 and MLKL. ROS levels were increased in the TZA group compared with the control group (27.74±1. IntroductionAcute kidney injury (AKI) is a common clinical syndrome that is characterized by the rapid loss of kidney function and abrupt kidney damage. It is associated with high morbidity and mortality worldwide (1). Acute tubular necrosis (ATN) is the most common and severe pathological manifestation of AKI. Although necrosis has long been considered to be unregulated, previous studies have revealed various types of regulated necrosis that are independent of caspase activities (2). Necroptosis is an important type of regulated necrosis and is involved in various pathological conditions (3-7). Receptor-interacting protein kinase (RIP)-1 receives signals from various death stimuli, and subsequently recruits RIP-3 via RIP homotypic interaction motif domain-mediated interactions and promotes RIP-3 phosphorylation (8,9). Phosphorylated RIP-3 mediates the phosphorylation of mixed-lineage kinase domain-like (MLKL), ultimately leading to rupture of the plasma membrane (7). Previous studies have identified necroptosis in ATN induced by various stimuli, including ischemia/reperfusion, contrast medium and cisplatin (10-12). RIP-1 inhibition by necrostatin-1 (Nec-1), or knockout of RIP-3 or MLKL all prevent ATN (10-12).Reactive oxygen species (ROS) promote necroptosis in cardiomyocytes, liver cells, Jurkat cells and lung adenoma cells (13)(14)(15)(16). However, the effect of ROS on the necroptosis of renal tubular epithelium remains unknown. The present study hypothesized that excessive ROS production may promote necroptosis in HK-2 human kidney cells. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, has been demonstrated to reduce ROS production and exert a protective role in numerous cell types (17)(18)(19)

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“…Indeed, overexpression of SIRT3 in THP-1 cells inhibited the activation of the NLRP3 inflammasome, whereas its knockdown stimulated its activation [91]. Not surprisingly, SIRT3 inhibits the NLRP3 inflammasome in a mouse model of sepsis-induced acute kidney injury by attenuating ROS production [92], and is also protective in a model of LPS-induced lethality [93]. SIRT3 deficiency accelerates the development of metabolic syndrome in mouse, and single nucleotide polymorphisms in the human SIRT3 gene have been associated with this condition [40].…”

Section: Sirtuins As Metabolic Sensors That Regulate Inflammationmentioning

confidence: 99%

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

Traba

Sack

2016

Cell. Mol. Life Sci.

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Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.

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Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

Cited by 86 publications

References 36 publications

Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy

Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy

NADPH oxidase inhibitor, diphenyleneiodonium prevents necroptosis in HK-2 cells

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

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