High-mobility group box 1 protein-mediated necroptosis contributes to dasatinib-induced cardiotoxicity

Xu, Zhifei; Jin, Ying; Hao, Yan; Gao, Zizheng; Xu, Bo; Yang, Bo; He, Qiaojun; Shi, Qiang; Luo, Peihua

doi:10.1016/j.toxlet.2018.08.003

Cited by 44 publications

(25 citation statements)

References 37 publications

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“…Moreover, the Nec-1 administration also reduced protein leakage that indicated impaired cellular membrane and the formation of inflammatory mediators. HMGB1, a well-recognized necroptosis marker [ 36 ] was significantly increased in the BAL fluid following IR and could be reduced by Nec-1 but not z-VAD-fmk treatment. These data supported the contribution of necroptosis to lung IR injury, and this was consistent with the results by Kanou T et al, who demonstrated that the Nec-1 administration to both donor and recipient could significantly inhibit necrotic cell death and improve graft function following lung transplantation in rats [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Necrostatin-1 Synergizes the Pan Caspase Inhibitor to Attenuate Lung Injury Induced by Ischemia Reperfusion in Rats

Wang

Chen

Xiong

et al. 2020

Mediators of Inflammation

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Background. Both apoptosis and necroptosis have been recognized to be involved in ischemia reperfusion-induced lung injury. We aimed to compare the efficacies of therapies targeting necroptosis and apoptosis and to determine if there is a synergistic effect between the two therapies in reducing lung ischemia reperfusion injury. Methods. Forty Sprague-Dawley rats were randomized into 5 groups: sham (SM) group, ischemia reperfusion (IR) group, necrostatin-1+ischemia reperfusion (NI) group, carbobenzoxy-Val-Ala-Asp-fluoromethylketone+ischemia reperfusion (ZI) group, and necrostatin-1+carbobenzoxy-Val-Ala-Asp-fluoromethylketone+ischemia reperfusion (NZ) group. The left lung hilum was exposed without being clamped in rats from the SM group, whereas the rats were subjected to lung ischemia reperfusion by clamping the left lung hilum for 1 hour, followed by reperfusion for 3 hours in the IR group. 1 mg/kg necrostatin-1 (Nec-1: a specific necroptosis inhibitor) and 3 mg/kg carbobenzoxy-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk: a pan caspase inhibitor) were intraperitoneally administrated prior to ischemia in NI and ZI groups, respectively, and the rats received combined administration of Nec-1 and z-VAD-fmk in the NZ group. Upon reperfusion, expressions of receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and caspase-8 were measured, and the flow cytometry analysis was used to assess the cell death patterns in the lung tissue. Moreover, inflammatory marker levels in the bronchoalveolar lavage fluid and pulmonary edema were evaluated. Results. Both Nec-1 and z-VAD-fmk, either alone or in combination, significantly reduced morphological damage, inflammatory markers, and edema in lung tissues following reperfusion, and cotreatment of z-VAD-fmk with Nec-1 produced the optimal effect. The rats treated with Nec-1 had lower levels of inflammatory markers in the bronchoalveolar lavage fluid than those receiving z-VAD-fmk alone ( P < 0.05 ). Interestingly, the z-VAD-fmk administration upregulated RIP1 and RIP3 expressions in the lung tissue from the ZI group compared to those in the IR group ( P < 0.05 ). Reperfusion significantly increased the percentages of necrotic and apoptotic cells in lung tissue single-cell suspension, which could be decreased by Nec-1 and z-VAD-fmk, respectively ( P < 0.05 ). Conclusions. Nec-1 synergizes the pan caspase inhibitor to attenuate lung ischemia reperfusion injury in rats. Our data support the potential use of Nec-1 in lung transplantation-related disorders.

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Section: Discussionmentioning

confidence: 99%

Necrostatin-1 Synergizes the Pan Caspase Inhibitor to Attenuate Lung Injury Induced by Ischemia Reperfusion in Rats

Wang

Chen

Xiong

et al. 2020

Mediators of Inflammation

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“…Cell survival was assessed with a sulforhodamine B colorimetric assay (SRB, #S1402, Sigma) [24]. Briefly, cell monolayers were fixed with 10% (wt/vol) trichloroacetic acid and stained for 30 min, after which the excess dye was removed by washing repeatedly with 1% (vol/vol) acetic acid.…”

Section: Cell Survival Assaymentioning

confidence: 99%

“…Quantitative real-time polymerase chain reaction analysis The quantitative polymerase chain reaction (qPCR) analysis was performed as described previously [24]. Total RNA isolation was carried out with an RNAiso Plus kit (#9109, TaKaRa, Japan) according to the manufacturer's instructions.…”

Section: Intracellular Gsh Concentration Determinationmentioning

confidence: 99%

Identification of PRDX6 as a regulator of ferroptosis

et al. 2019

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Ferroptosis is a newly characterized iron-dependent form of nonapoptotic regulated cell death triggered by lipid reactive oxygen species (LOOH). The dysregulation of ferroptosis is highly related to cancer, and the induction of ferroptosis is also proposed as a potential strategy for cancer therapy. Although several key regulators have been identified that are involved in ferroptosis, the molecular mechanism underlying this process remains largely unknown. Here, we report that Peroxiredoxin-6 (PRDX6) is a bona fide negative regulator of ferroptotic cell death. The knockdown of intracellular PRDX6 significantly enhances LOOH and ferroptotic cell death triggered by ferroptosis inducers (Erastin and RSL-3), which is correlated with the transcriptional activation of heme oxygenase-1. Moreover, overexpression of heme oxygenase-1 enhances both Erastin-and RSL-3-triggered LOOH, suggesting that heme oxygenase-1 mediates PRDX6 silencing-enhanced ferroptosis. More importantly, the application of a specific PRDX6 phospholipase A2 (iPLA2) inhibitor, MJ-33, synergistically enhances the ferroptosis induced by Erastin, suggesting that PRDX6 removes LOOH through its iPLA2 activity. Thus, our findings reveal an essential role of PRDX6 in protecting cells against ferroptosis and provide a potential target to improve the antitumor activity of ferroptosis-based chemotherapy.

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“…The DAMPs that are secreted/released upon necroptosis include: (I) "find me" signals (as described above); (II) intracellular chaperones such as heat-shock proteins (HSPs) [160] and S100 protein family members; (III) alarmins or cytokine-like DAMPs [161] and (IV) nucleic acids (nuclear or mitochondrial DNA) [162]. One of the most ubiquitous alarmins released during necroptosis is the high mobility group box 1 (HMGB1) protein [63,163,164]. These DAMPs usually stimulate the initial sensors of infection or damage, i.e., PRRs on myeloid cells, thereby efficiently co-stimulating them and enabling a better interface between these activated myeloid cells and adaptive immune cells [165].…”

Section: Necroptosis-driven Modulation Of Immune Responsesmentioning

confidence: 99%

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

Sprooten

Wijngaert

Vanmeerbeek

et al. 2020

Cells

132

112

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Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy.

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High-mobility group box 1 protein-mediated necroptosis contributes to dasatinib-induced cardiotoxicity

Cited by 44 publications

References 37 publications

Necrostatin-1 Synergizes the Pan Caspase Inhibitor to Attenuate Lung Injury Induced by Ischemia Reperfusion in Rats

Necrostatin-1 Synergizes the Pan Caspase Inhibitor to Attenuate Lung Injury Induced by Ischemia Reperfusion in Rats

Identification of PRDX6 as a regulator of ferroptosis

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

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