CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis

Zhang, Ting; Zhang, Yan; Cui, Mingyao; Jin, Li; Wang, Yimei; Lv, Fengxiang; Liu, Yuli; Zheng, Wen; Shang, Haibao; Zhang, Jun; Zhang, Mao; Wu, Hong-Kun; Guo, Jiaojiao; Zhang, Xiuqin; Hu, Xinli; Cao, Chunmei; Xiao, Rui‐Ping

doi:10.1038/nm.4017

Cited by 648 publications

(704 citation statements)

References 57 publications

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“…Pertinent to the present study, necroptosis has been recognized as a key cell death pathway in cardiomyocytes during ischemia-reperfusion injury and acute coronary syndromes (24)(25)(26).…”

Section: Introductionsupporting

confidence: 53%

See 1 more Smart Citation

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Reyes

Restrepo

Hinojosa

et al. 2017

Am J Respir Crit Care Med

117

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“…Pertinent to the present study, necroptosis has been recognized as a key cell death pathway in cardiomyocytes during ischemia-reperfusion injury and acute coronary syndromes (24)(25)(26).…”

Section: Introductionsupporting

confidence: 53%

“…Cardiomyocytes have been shown to die by apoptosis or necroptosis during injury or disease (24)(25)(26). Apoptosis is an immunoquiescent form of cell death that requires the activity of cysteine proteases known as caspases (42).…”

Section: Discussionmentioning

confidence: 99%

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Reyes

Restrepo

Hinojosa

et al. 2017

Am J Respir Crit Care Med

117

View full text Add to dashboard Cite

“…RIP3 co‐localized with mitochondria when necrosis was induced in a kinase activity‐dependent manner and promoted mitochondrial metabolism and ROS production by activating the PYGL, GLUL and GLUD1, leading to the consequent necrosis as mentioned above (Figures 3 and 4). 60 In a recent study, Ting Zhang et al found that siRNA‐mediated knockdown of Cypd markedly alleviated RIP3‐induced cardiomyocyte necrosis as assessed by cellular ATP content and LDH release, further revealing the close relationship between these 2 pathways 61…”

Section: Signalling Interactionmentioning

confidence: 98%

Molecular mechanism and therapy application of necrosis during myocardial injury

Ding

Tariq

et al. 2018

J Cellular Molecular Medi

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Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new pharmacological application in the treatment of heart diseases. In this review, we summarize the advanced progress in these signalling pathways and discuss the pathos‐physiological relevance and therapeutic implication of targeting necrosis in heart diseases treatment.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

mentioning

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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CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis

Cited by 648 publications

References 57 publications

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Molecular mechanism and therapy application of necrosis during myocardial injury

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

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