Resveratrol inhibits necroptosis by mediating the TNF-&amp;alpha;/RIP1/RIP3/MLKL pathway in myocardial hypoxia/reoxygenation injury

Hu, Yongjun; Peng, Jianqiang; He, Jin; Tang, Mingxiang; Yan, Sulan; Rong, Jingjing; Li, Junshan; Zheng, Zhaofen; Wang, Haijun; Liu, Yanfu; Zhong, Xin

doi:10.1093/abbs/gmab012

Cited by 27 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the RIP1/RIP3 pathway is a significant signaling pathway which is responsible for regulating cell viability and necroptosis in renal IRI 22 , TNFα is a classic inflammatory cytokine, but a familiar inducer of necroptosis in some pathological process, particularly in the disease containing inflammation and necrosis 23 . Inhibition of caspase8 can also induce necroptosis of renal tubular epithelial cells 17 .…”

Section: Resultsmentioning

confidence: 99%

MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

Ke¹,

Zhao²,

Luo³

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Renal ischemia-reperfusion injury (IRI) is one of the underlying causes of acute kidney injury and also an unavoidable problem in renal transplantation. Lots of miRNAs and targets have been found to participate in some post-transcriptional processes in renal IRI, however, the detailed knowledge of miRNA targets and mechanism is unknown. In this study, miR-124 was found inhibited and PARP1 was overexpressed in renal IRI cells and mouse models. Dual-luciferase reporter assay revealed that miR-124 post-transcriptionally regulated PAPR1 3′UTR activity. Our results also demonstrated miR-124 negatively regulated PARP1 which played a role in necroptosis of renal ischemia-reperfusion injury by activating TNFα. TNFα induced the RIP1/RIP3 necroptosis signaling pathway to aggravate the renal injury. Collectively, these studies identified PARP1 as a direct target of miR-124 and activated RIP1/RIP3 necroptosis signaling pathway through TNFα. It elucidated the protective effect of miR-124 in renal ischemia-reperfusion injury, which demonstrated the regulatory mechanism of miR-124/PARP1 in renal injury and exhibited the potential as a novel therapeutic for the treatment of renal IRI.

show abstract

Section: Resultsmentioning

confidence: 99%

MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

Ke¹,

Zhao²,

Luo³

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Moreover, our results showed that the levels of RIPK3, RIPK1 and MLKL were promoted during progression of ARHL. Previous, Hu et al revealed that RSV suppresses necroptosis in H9c2 cells, which may realize through the inhibition of the TNF-α/RIP1/RIP3/MLKL signaling pathway ( Hu et al, 2021 ). Consistently, our data depicted that the protein expressions of RIPK1, RIPK3, and MLKL in cochlea tissues were sharply decreased after administration of 50 mg/kg RSV.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss

et al. 2022

View full text Add to dashboard Cite

Background: To investigate the pathophysiology of age-related hearing loss (ARHL) and the mechanism of resveratrol (RSV) in prevention and treatment of ARHL.Methods: C57BL/6 mice of different ages were used in this study. Auditory brainstem response (ABR) was performed to assess hearing and identify abnormalities. Surface preparation and hair cell-specific marker Myo VIIa were employed to evaluated cochlear hair cell losses. Scanning electron microscopy (SEM) was to observe the microstructure of the organ of Corti (OC). The expression of related proteins in the RIPK1/RIPK3/MLKL pathway in cochlear tissue was detected by immunofluorescence.Results: In old mice (15 months), the ABR threshold increased significantly compared with the young mice. After 50 mg/kg RSV intervention, the hearing threshold of the old mice was significantly reduced at 8 kHz and 12 kHz as well as click. 100 mg/kg RSV led to a statistically significant reduction in hearing threshold only at clicks, whereas 300 mg/kg RSV showed no difference at all frequencies tested. In terms of cochlear hair cell loss, the damage of OHC and IHC was severe in old mice, but the damage was evidently reduced in RSV 50 mg/kg group. Notably, in the RSV 300 mg/kg group, the loss and disorientation of both the OHCs and IHCs were aggravated. Under SEM, a large number of OHCs were lost in the old group, but increased significantly in the RSV 50 mg/kg group, and even the OHCs were more seriously damaged in the RSV 300 mg/kg group. Furthermore, immunofluorescence showed that 50 mg/kg RSV significantly reduced the expression of RIPK3, RIPK1, and MLKL in the cochlea during aging, especially in necroptosis-sensitive regions OCs and SGN.Conclusion: Low-dose RSV inhibited RIPK3-mediated necroptosis in aging cochlea and delayed the onset of ARHL, which was a promising therapeutic strategy for ARHL.

show abstract

“…Furthermore, tumor necrosis factor- α (TNF- α ) has been reported to play a key role in the initiation of necrosis and the induction of stimulated necrosis. TNF- α can activate cell suicide mechanisms, such as apoptosis and necrosis, and trigger the accumulation and phosphorylation of RIPK1 and RIPK3, resulting in the phosphorylation of MLKL, the formation of necrotic bodies, and necrosis [ 30 ]. Moreover, recent studies have identified that the elevated levels of necroptosis is accompanied by an increase in pro-inflammatory cytokines IL-6 and TNF- α (3.9-4.7-fold) in addition to an increase in the level of oxidative stress [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Ca2+/Calmodulin-Dependent Protein Kinase II Regulation by Inhibitor of RIPK3 Protects against Cardiac Hypertrophy

Zhang

Qian

Cao

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The activity of Ca2+/calmodulin-dependent protein kinase II δ (CaMKII δ) is central to the mechanisms of cardiovascular diseases. Receptor-interacting protein kinase 3- (RIPK3-) mediated necroptosis has been reported to contribute to cardiac dysfunction. However, the potential protective role of inhibition of RIPK3, a regulator of CaMKII, on cardiac hypertrophy remains unclear. The present study is aimed at investigating how the RIPK3 inhibitor GSK’872 regulates CaMKII activity and exploring its effect on hypertrophic cardiomyopathy (HCM). Wild-type (WT) and RIPK3 gene knockout (RIPK3-/-) mice were implanted subcutaneously with Alzet miniosmotic pumps (200 μL) and perfused with angiotensin II (AMP-AngII) to induce cardiac hypertrophy. After WT mice were induced by AngII for 72 hours, they were injected with GSK’872 with an intraperitoneal (IP) dose of 6 mg/kg once a day for two weeks. After this, they were physiologically examined for Echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK3 expression, mixed lineage kinase domain-like protein (MLKL) phosphorylation, and mitochondrial ultrastructure. The results indicated that deletion of the RIPK3 gene or administration of GSK’872 could reduce CaMKII activity, alleviate oxidative stress, reduce necroptosis, and reverse myocardial injury and cardiac dysfunction caused by AngII-induced cardiac hypertrophy in mice. The present study demonstrated that CaMKII activation and necroptosis augment cardiac hypertrophy in a RIPK3-dependent manner, which may provide therapeutic strategies for HCM. RIPK3 inhibitor GSK’872 has a protective effect on cardiac hypertrophy and could be an efficacious targeted medicine for HCM in clinical treatment.

show abstract

Resveratrol inhibits necroptosis by mediating the TNF-α/RIP1/RIP3/MLKL pathway in myocardial hypoxia/reoxygenation injury

Cited by 27 publications

References 33 publications

MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss

Ca2+/Calmodulin-Dependent Protein Kinase II Regulation by Inhibitor of RIPK3 Protects against Cardiac Hypertrophy

Contact Info

Product

Resources

About