Cadmium induces NLRP3 inflammasome-dependent pyroptosis in vascular endothelial cells

Chen, Haiyan; Lu, Yonghui; Cao, Zhengwang; Ma, Qibin; Pi, Huifeng; Fang, Yiliang; Yu, Zhengping; Hu, Houxiang; Zhou, Zhou

doi:10.1016/j.toxlet.2016.01.014

Cited by 144 publications

(79 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data suggest that KCNQ1OT1 may promote pyroptosis in cataracts due to its ability to inhibit miR-214 and subsequent activation of caspase-1. Caspase-1 is an important marker in the development of pyroptosis [34]. In this study, we found that KCNQ1OT1 expression in normal lens anterior capsule tissues is remarkably lower than that in cataract lens anterior capsule tissues.…”

Section: Discussionmentioning

confidence: 52%

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Jin

Hao²,

Shi

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. Methods: Human lens epithelium cells (HLECs) were treated with H 2 O 2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR. The expression of caspase-1 was detected using qRT-PCR, western blot and immunostaining. To confirm our findings in cell cultures, we analysed KCNQ1OT1, miR-214, and caspase-1 expression in lens anterior capsules of both cataract patients and normal controls by qRT-PCR and western blot analysis. Results: We found that the expression of KCNQ1OT1 was increased in both human cataract lens anterior capsular samples and SRA01/04 cell lines treated with H 2 O 2 . Knockdown of KCNQ1OT1 expression significantly suppressed H 2 O 2 -induced SRA01/04 cell pyroptosis in vitro, which is the critical step in cataract formation. The expression of microRNA-214 (miR-214) was also decreased in cataract lens anterior capsular tissues and H 2 O 2 -induced SRA01/04 cell lines. Knockdown of KCNQ1OT1 significantly increased the expression of miR-214. Conclusions: We demonstrated for the first time that caspase-1 is a functional downstream target of miR-214, and knockdown of KCNQ1OT1 reduced the expression of caspase-1. These results provide evidence that the KCNQ1OT1-miR-214-caspase-1 regulatory network is a novel mechanism for promoting cataract formation.

show abstract

Section: Discussionmentioning

confidence: 52%

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Jin

Hao²,

Shi

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Consistent with the changes in liver function, the histopathological analysis showed that exposure to Cd resulted in hepatocyte swelling and necrosis, mild inflammatory infiltration, and hemorrhage (Figure D‐E). Our previous study demonstrated that Cd induced cell death in vascular endothelial cells . To assess whether Cd induces hepatocyte death, we treated primary hepatocytes with 10 μ mol L −1 Cd for different lengths of time (0, 3, 6, and 12 hours).…”

Section: Resultsmentioning

confidence: 99%

Melatonin alleviates cadmium‐induced liver injury by inhibiting the TXNIP‐NLRP3 inflammasome

Cao

Fang

et al. 2017

Journal of Pineal Research

Self Cite

172

View full text Add to dashboard Cite

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death. Male C57BL/6 mice were intraperitoneally injected with melatonin (10 mg/kg) once a day for 3 days before exposure to CdCl (2.0 mg/kg). We found that Cd induced hepatocellular damage and inflammatory infiltration as well as increased serum ALT/AST enzymes. In addition, we showed that Cd triggered an inflammatory cell death, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, melatonin treatment significantly alleviated Cd-induced liver injury by decreasing serum ALT/AST levels, suppressing pro-inflammatory cytokine production, inhibiting NLRP3 inflammasome activation, ameliorating oxidative stress, and attenuating hepatocyte death. Most importantly, melatonin markedly abrogated Cd-induced TXNIP overexpression and decreased the interaction between TXNIP and NLRP3 in vivo and in vitro. However, treatment with siRNA targeting TXNIP blocked the protective effects of melatonin in Cd-treated primary hepatocytes. Collectively, our results suggest that melatonin confers protection against Cd-induced liver inflammation and hepatocyte death via inhibition of the TXNIP-NLRP3 inflammasome pathway.

show abstract

“…Indeed, although controversial, many studies have used relatively direct and exact methods to detect pyroptosis such as double staining cells with FAM-YVAD-FMK (a marker of activated Caspase-1) and PI or SYTOX Blue DNA intercalation staining (a marker of pore formation in the plasma membrane). 30, 32 Detection of LDH release (as a marker of pore formation in the plasma membrane) is also used widely to identify pyroptosis. 32 Some labs like Jiahuai et al 's and Lei et al 's also have made great efforts to explore the morphologic characteristics of pyroptosis by electron microscopy and have made certain achievements recently that may contribute to the future detection of pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

“…30, 32 Detection of LDH release (as a marker of pore formation in the plasma membrane) is also used widely to identify pyroptosis. 32 Some labs like Jiahuai et al 's and Lei et al 's also have made great efforts to explore the morphologic characteristics of pyroptosis by electron microscopy and have made certain achievements recently that may contribute to the future detection of pyroptosis. 30, 33 In this study, detection of active caspase 1 and PI double stain were used in combination with an LDH release assay to detect and quantify pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages

et al. 2017

View full text Add to dashboard Cite

A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation.

show abstract

Cadmium induces NLRP3 inflammasome-dependent pyroptosis in vascular endothelial cells

Cited by 144 publications

References 51 publications

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway

Melatonin alleviates cadmium‐induced liver injury by inhibiting the TXNIP‐NLRP3 inflammasome

NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages

Contact Info

Product

Resources

About