Necroptosis signaling in liver diseases: An update

Saeed, Waqar Khalid; Jun, Dae Won; Jang, Kiseok; Koh, Dong Hee

doi:10.1016/j.phrs.2019.104439

Cited by 42 publications

(48 citation statements)

References 98 publications

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“…As mentioned above, necroptosis is a recently discovered type of RCD, which, in contrast to apoptosis, is characterized by morphological features of necrosis [2]. In fact, an increasingly translucent cytoplasm, the swelling of organelles, lysosomal membrane permeabilization, and an enlarged cell volume are common features of necroptosis.…”

Section: Necroptosismentioning

confidence: 99%

“…The contribution of necroptosis to liver disease seems to be context-specific and dependent on the lineage of the involved cells, the etiology, the stage of the disease, and the nature and extent of co-morbidities [59,60]. Various methods, including pharmacological inhibition and gene knockout and knockdown, have been utilized to evaluate the role of necroptosis in different diseases, mostly using murine models [2,54]. As a model of acute liver injury, several groups focused on acetaminophen-induced hepatic injury (AIHI) in mice, but the results they obtained were conflicting [2,3,18,57,58,[61][62][63][64][65][66][67][68].…”

Section: Overview On Necroptosis In Liver Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Necroptosis is a type of tightly regulated cell death (RCD) mimicking the morphological features of necrosis [2]. Similar to non-regulated necrosis, it represents an inflammatory mode of CD [2]. Necroptosis and its molecular players contribute to embryonic and post-natal development and participate in tissue homeostasis [2].…”

Section: Introductionmentioning

confidence: 99%

“…Similar to non-regulated necrosis, it represents an inflammatory mode of CD [2]. Necroptosis and its molecular players contribute to embryonic and post-natal development and participate in tissue homeostasis [2]. Several studies on cell lines, animal models, and human tissue have been conducted over the last ten years, demonstrating the involvement of necroptosis in the pathogenesis and natural course of different pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

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Necroptosis in Cholangiocarcinoma

Sarcognato

Jong

Fabris

et al. 2020

Cells

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Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.Cells 2020, 9, 982 2 of 18 (RIPK3) and mixed lineage kinase domain-like (MLKL) [4]. Therefore, necroptosis is an alternative mode of CD when the caspase-8-dependent apoptotic pathway is blocked. It is now well-established that various stimuli can initiate necroptosis, including intra-and extracellular factors, such as tumor necrosis factor α (TNFα) and reactive oxygen species (ROS) [5].A hallmark of cancer is the ability of malignant cells to evade apoptosis. Therefore, the induction of necroptosis could be an alternative strategy for killing cancer cells. Several therapeutics able to affect the necroptotic cascade have recently been developed, and a few of them are already in phase 1 trials for the treatment of inflammatory diseases. Moreover, necroptosis modulation is becoming the target of several new anti-cancer strategies. In fact, it has been demonstrated that apoptosis-resistant tumors respond to necroptosis, and that necroptosis can create an immunogenic microenvironment that enhances tumor clearance [6]. These aspects will be further discussed in the following chapters.Herein, we will discuss the general aspects of necroptosis and what is currently known on its involvement in cholangiocarcinoma (CCA), in order to provide perspectives for future studies in this relatively new field. Overview on Types of Cell DeathIn 2005, the Nomenclature Committee on Cell Death (NCCD) defined the first CD classification purely based on morphological criteria. This classification included three major forms of CD: types I, II, and III [7]. Type I CD, termed apoptosis, exhibits cell shrinkage, membrane blebbing, DNA fragmentation, chromatin condensation, and the formation of apoptotic bodies. Apoptosis is a form of RCD and responds to two different death signals: damage from inside the cell, such as DNA damage, which elicits an intrinsic pathway, and extracellular stimuli, such as TNFα and the Fas ligand, ...

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Section: Necroptosismentioning

confidence: 99%

Section: Overview On Necroptosis In Liver Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Necroptosis in Cholangiocarcinoma

Sarcognato

Jong

Fabris

et al. 2020

Cells

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The HSP90 inhibitor 17‐DMAG alleviates primary biliary cholangitis via cholangiocyte necroptosis prevention

Chen

Fan

Chu

et al. 2022

J of Cellular Biochemistry

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Cholangiocyte death accompanied by the progression of primary biliary cholangitis (PBC) has not yet been thoroughly investigated. Thus, we are aimed to explore the role of HSP90 and a potential treatment strategy in cholangiocyte necroptosis. First, we detected the expression of HSP90 and necroptotic markers in liver tissues from patients and mice with PBC by immunohistochemistry (IHC) and real‐time polymerase chain reaction (PCR). Then, the HSP90 inhibitor, 17‐dimethylaminoethylamino‐17‐demethoxygeldanamycin (17‐DMAG), was administered by intraperitoneal injection to evaluate its therapeutic effect for PBC by IHC, real‐time PCR, and western blotting. Human intrahepatic bile duct epithelial cells (HIBECs) were induced to necroptosis by toxic bile acid and lipopolysaccharide (LPS) treatment, and evaluated via Cell Counting Kit‐8 and flow cytometry assays. Additionally, 17‐DMAG, cycloheximide, and a proteasome inhibitor were used to evaluate the role of HSP90 in cholangiocyte necroptosis. We found that the expression of HSP90 was elevated in the cholangiocytes of patients and mice with PBC, along with higher expressions of receptor‐interacting serine/threonine‐protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain‐like protein (MLKL), and phosphorylated‐MLKL (p‐MLKL). Proinflammatory cytokines and antibody levels of the E2 subunit of pyruvate dehydrogenase complex decreased after treatment with 17‐DMAG in PBC mice. Meanwhile, RIPK1, RIPK3, phosphorylated‐RIPK3, MLKL, and p‐MLKL protein expressions decreased with 17‐DMAG treatment. In vitro, 17‐DMAG and necrostatin‐1 prevented glycochenodeoxycholic acid and LPS‐induced necroptosis of HIBECs. Immunoprecipitation and high‐performance liquid chromatography–mass spectrometry analysis showed that RIPK1 combined with HSP90. Additionally, the 17‐DMAG treatment reduced the RIPK1 half‐life. Overall, 17‐DMAG might be a potential therapeutic agent for PBC via cholangiocyte necroptosis prevention by accelerating RIPK1 degradation.

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