scholarly journals Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury

Hepatology ◽  
2013 ◽  
Vol 57 (5) ◽  
pp. 1773-1783 ◽  
Author(s):  
Sanjoy Roychowdhury ◽  
Megan R. McMullen ◽  
Sorana G. Pisano ◽  
Xiuli Liu ◽  
Laura E. Nagy
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Interacting Protein

scholarly journals Necrostatin-1 accelerates time to death in a rat model of cecal ligation and puncture and massively increases hepatocyte caspase-3 cleavage

2019 ◽  
Vol 316 (4) ◽  
pp. G551-G561 ◽  
Author(s):  
Qin Zhang ◽  
Siwei Wei ◽  
Jiayin Lu ◽  
Weijun Fu ◽  
Hui Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Survival Time ◽  
Caspase 3 ◽  
Cecal Ligation ◽  
B Cell Lymphoma ◽  
Cecal Ligation And Puncture ◽  
Interacting Protein ◽  
Regulated Necrosis ◽  
Related Proteins

Necroptosis, a form of regulated necrosis, has been reported to be involved in numerous pathologies, including sepsis. However, a protective effect of the selective inhibitor of necroptosis, necrostatin-1 (Nec-1), against sepsis remains to be confirmed. Animals (rats and mice) were subjected to cecal ligation and puncture (CLP) to mimic clinical sepsis. Nec-1 or its vehicle (control) was administered 20 min before CLP. Survival time was observed up to 72 h after CLP. Specimens of liver tissue and serum were obtained at 6 h, 12 h, and 18 h. Expression of necroptosis-related proteins [receptor-interacting protein kinase (RIP)1, RIP3, and mixed lineage kinase domain-like (MLKL)] was determined by Western blot analysis. The RIP1/RIP3 interaction and the recruitment of MLKL to RIP3 were also analyzed. Liver function, histopathological changes, serum inflammation cytokines, TUNEL staining, and the expression of apoptosis-related protein, including caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (Bax), was determined. As expected, Nec-1 administration reduced the expression of necroptosis-related proteins and the RIP1/RIP3 interaction, indicating inhibited necroptosis. Surprisingly, Nec-1 treatment exacerbated the liver injury and shortened survival time of septic rats with increased TUNEL-positive cells, cleaved caspase-3 protein content, and Bax/Bcl-2 ratio. Collectively, these findings show that Nec-1 administration inhibited the hepatocyte necroptosis pathway but accelerated apoptosis via the apoptotic pathway in CLP-induced sepsis rat. NEW & NOTEWORTHY The present study demonstrated that a chemical inhibitor necrostatin-1 (Nec-1) or receptor-interacting protein kinase(RIP1) knock down targeted at necroptosis inhibition accelerated liver injury of following sepsis. For fundamental research, these results warrant further investigation of the potential link between Nec-1 administration and the cellular apoptosis following sepsis induced liver injury. For applied research, these results suggest the potential harmful effect of Nec-1 on future sepsis treatment.

scholarly journals The role of the c-Jun N-terminal kinases 1/2 and receptor-interacting protein kinase 3 in furosemide-induced liver injury

Xenobiotica ◽  
2014 ◽  
Vol 45 (5) ◽  
pp. 442-449 ◽  
Author(s):  
Mitchell R. McGill ◽  
Kuo Du ◽  
Yuchao Xie ◽  
Mary Lynn Bajt ◽  
Wen-Xing Ding ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Interacting Protein

scholarly journals Yi-Qi-Jian-Pi Formula Suppresses RIPK1/RIPK3-Complex-Dependent Necroptosis of Hepatocytes Through ROS Signaling and Attenuates Liver Injury in Vivo and in Vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Feixia Wang ◽  
Li Tang ◽  
Baoyu Liang ◽  
Chun Jin ◽  
Liyuan Gao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Protective Effect ◽  
Molecular Mechanisms ◽  
Positive Role ◽  
Interacting Protein ◽  
Ros Signaling ◽  
Tnf Α

Acute-on-chronic liver failure (ACLF) is described as a characteristic of acute jaundice and coagulation dysfunction. Effective treatments for ACLF are unavailable and hence are urgently required. We aimed to define the effect of Yi-Qi-Jian-Pi Formula (YQJPF) on liver injury and further examine the molecular mechanisms. In this study, we established CCl4-, LPS-, and d-galactosamine (D-Gal)-induced ACLF rat models in vivo and LPS- and D-Gal-induced hepatocyte injury models in vitro. We found that YQJPF significantly ameliorates liver injury in vivo and in vitro that is associated with the regulation of hepatocyte necroptosis. Specifically, YQJPF decreased expression of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and pseudokinase mixed lineage kinase domain-like (MLKL) to inhibit the migration of RIPK1 and RIPK3 into necrosome. YQJPF also reduces the expression of inflammatory cytokines IL-6, IL-8, IL-1β, and TNF-α, which were regulated by RIPK3 mediates cell death. RIPK1 depletion was found to enhance the protective effect of YQJPF. Furthermore, we showed that YQJPF significantly downregulates the mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarization, with ROS scavenger, 4-hydroxy-TEMPO treatment recovering impaired RIPK1-mediated necroptosis and reducing the expression of IL-6, IL-8, IL-1β, and TNF-α. In summary, our study revealed the molecular mechanism of protective effect of YQJPF on hepatocyte necroptosis, targeting RIPK1/RIPK3-complex-dependent necroptosis via ROS signaling. Overall, our results provided a novel perspective to indicate the positive role of YQJPF in ACLF.

scholarly journals Receptor Interacting Protein Kinase 3 Deficiency Exacerbates Cholestatic Liver Injury in Mice

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Benjamin Woolbright ◽  
C Williams ◽  
Mary‐Lynn Bajt ◽  
Wen‐Xing Ding ◽  
Hartmut Jaeschke
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Interacting Protein ◽  
Cholestatic Liver Injury

scholarly journals Overexpression of homeodomain-interacting protein kinase 2 (HIPK2) attenuates sepsis-mediated liver injury by restoring autophagy

2018 ◽  
Vol 9 (9) ◽  
Author(s):  
Zhengyu Jiang ◽  
Lulong Bo ◽  
Yan Meng ◽  
Chen Wang ◽  
Tianxing Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Interacting Protein

scholarly journals Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 17681-17698 ◽  
Author(s):  
Shaogui Wang ◽  
Hong-Min Ni ◽  
Kenneth Dorko ◽  
Sean C. Kumer ◽  
Timothy M. Schmitt ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Interacting Protein

Early signalling events of autophagy

2013 ◽  
Vol 55 ◽  
pp. 1-15 ◽  
Author(s):  
Laura E. Gallagher ◽  
Edmond Y.W. Chan
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Mammalian Cells ◽  
Mammalian Target Of Rapamycin ◽  
Interacting Protein ◽  
The Core ◽  
Autophagy Gene ◽  
Autophagy Induction ◽  
Cellular Pathways

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.

scholarly journals Pseudomonas syringae Effector AvrPphB Suppresses AvrB-Induced Activation of RPM1 but Not AvrRpm1-Induced Activation

2015 ◽  
Vol 28 (6) ◽  
pp. 727-735 ◽  
Author(s):  
Andrew R. Russell ◽  
Tom Ashfield ◽  
Roger W. Innes
Keyword(s):  
Disease Resistance ◽  
Protein Kinase ◽  
Molecular Mechanism ◽  
Pseudomonas Syringae ◽  
Hypersensitive Response ◽  
Hypersensitive Resistance ◽  
Nicotiana Glutinosa ◽  
Resistance Response ◽  
Interacting Protein ◽  
Soybean Plants

The Pseudomonas syringae effector AvrB triggers a hypersensitive resistance response in Arabidopsis and soybean plants expressing the disease resistance (R) proteins RPM1 and Rpg1b, respectively. In Arabidopsis, AvrB induces RPM1-interacting protein kinase (RIPK) to phosphorylate a disease regulator known as RIN4, which subsequently activates RPM1-mediated defenses. Here, we show that AvrPphB can suppress activation of RPM1 by AvrB and this suppression is correlated with the cleavage of RIPK by AvrPphB. Significantly, AvrPphB does not suppress activation of RPM1 by AvrRpm1, suggesting that RIPK is not required for AvrRpm1-induced modification of RIN4. This observation indicates that AvrB and AvrRpm1 recognition is mediated by different mechanisms in Arabidopsis, despite their recognition being determined by a single R protein. Moreover, AvrB recognition but not AvrRpm1 recognition is suppressed by AvrPphB in soybean, suggesting that AvrB recognition requires a similar molecular mechanism in soybean and Arabidopsis. In support of this, we found that phosphodeficient mutations in the soybean GmRIN4a and GmRIN4b proteins are sufficient to block Rpg1b-mediated hypersensitive response in transient assays in Nicotiana glutinosa. Taken together, our results indicate that AvrB and AvrPphB target a conserved defense signaling pathway in Arabidopsis and soybean that includes RIPK and RIN4.

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