Over the recent years, our understanding of the cell death machinery of mature erythrocytes has been greatly expanded. It resulted in the discovery of several regulated cell death (RCD) pathways in red blood cells. Apoptosis (eryptosis) and necroptosis of erythrocytes share certain features with their counterparts in nucleated cells, but they are also critically different in particular details. In this review article, we summarize the cell death subroutines in the erythroid precursors (apoptosis, necroptosis, and ferroptosis) in comparison to mature erythrocytes (eryptosis and erythronecroptosis) to highlight the consequences of organelle clearance and associated loss of multiple components of the cell death machinery upon erythrocyte maturation. Recent advances in understanding the role of erythrocyte RCDs in health and disease have expanded potential clinical applications of these lethal subroutines, emphasizing their contribution to the development of anemia, microthrombosis, and endothelial dysfunction, as well as their role as diagnostic biomarkers and markers of erythrocyte storage-induced lesions. Fas signaling and the functional caspase-8/caspase-3 system are not indispensable for eryptosis, but might be retained in mature erythrocytes to mediate the crosstalk between both erythrocyte-associated RCDs. The ability of erythrocytes to switch between eryptosis and necroptosis suggests that their cell death is not a simple unregulated mechanical disintegration, but a tightly controlled process. This allows investigation of eventual pharmacological interventions aimed at individual cell death subroutines of erythrocytes.
- MeSH
- apoptóza MeSH
- buněčná smrt MeSH
- eryptóza * MeSH
- erytrocyty * metabolismus cytologie MeSH
- ferroptóza MeSH
- lidé MeSH
- nekroptóza MeSH
- regulovaná buněčná smrt MeSH
- signální transdukce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Eryptosis is a regulated cell death (RCD) of mature erythrocytes initially described as a counterpart of apoptosis for enucleated cells. However, over the recent years, a growing number of studies have emphasized certain differences between both cell death modalities. In this review paper, we underline the hallmarks of eryptosis and apoptosis and highlight resemblances and dissimilarities between both RCDs. We summarize and critically discuss differences in the impact of caspase-3, Ca2+ signaling, ROS signaling pathways, opposing roles of casein kinase 1α, protein kinase C, Janus kinase 3, cyclin-dependent kinase 4, and AMP-activated protein kinase to highlight a certain degree of divergence between apoptosis and eryptosis. This review emphasizes the crucial importance of further studies that focus on deepening our knowledge of cell death machinery and identifying novel differences between cell death of nucleated and enucleated cells. This might provide evidence that erythrocytes can be defined as viable entities capable of programmed cell destruction. Additionally, the revealed cell type-specific patterns in cell death can facilitate the development of cell death-modulating therapeutic agents.
Hemocompatibility evaluation is an important step in nanotoxicological studies. It is generally accepted that nanomaterials promote lysis of erythrocytes, blood clotting, alter phagocytosis, and upregulate pro-inflammatory cytokines. However, there are no standardized guidelines for testing nanomaterials hemocompatibility despite the fact that nanomaterials enter the bloodstream and interact with blood cells. In this review, the current knowledge on the ability of nanomaterials to induce distinct cell death modalities of erythrocytes is highlighted primarily focusing on hemolysis and eryptosis. This review aims to summarize the molecular mechanisms underlying erythrotoxicity of nanomaterials and critically compare the sensitivity and efficiency of hemolysis or eryptosis assays for nanomaterials blood compatibility testing. The list of eryptosis-inducing nanomaterials is growing, but it is still difficult to generalize how physico-chemical properties of nanoparticles affect eryptosis degree and molecular mechanisms involved. Thus, another aim of this review is to raise the awareness of eryptosis as a nanotoxicological tool to encourage the corresponding studies. It is worthwhile to consider adding eryptosis to in vitro nanomaterials hemocompatibility testing protocols and guidelines.
- MeSH
- eryptóza * účinky léků MeSH
- erytrocyty účinky léků MeSH
- hemolýza * účinky léků MeSH
- lidé MeSH
- nanostruktury * toxicita MeSH
- testování materiálů metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Necroptosis is considered a programmed necrosis that requires receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and pore-forming mixed lineage kinase domain-like protein (MLKL) to trigger a regulated cell membrane lysis. Membrane rupture in necroptosis has been shown to fuel innate immune response due to release of damage-associated molecular patterns (DAMPs). Recently published studies indicate that mature erythrocytes can undergo necroptosis as well. In this review, we provide an outline of multiple cell death modes occurring in erythrocytes, discuss possible immunological aspects of diverse erythrocyte cell deaths, summarize available evidence related to the ability of erythrocytes to undergo necroptosis, outline key involved molecular mechanisms, and discuss the potential implication of erythrocyte necroptosis in the physiology and pathophysiology. Furthermore, we aim to highlight the interplay between necroptosis and eryptosis signaling in erythrocytes, emphasizing specific characteristics of these pathways distinct from their counterparts in nucleated cells. Thus, our review provides a comprehensive summary of the current knowledge of necroptosis in erythrocytes. To reflect critical differences between necroptosis of nucleated cells and necroptosis of erythrocytes, we suggest a term erythronecroptosis for necroptosis of enucleated cells.
- MeSH
- eryptóza MeSH
- erytrocyty * metabolismus patologie MeSH
- lidé MeSH
- nekroptóza * MeSH
- nekróza MeSH
- proteinkinasy metabolismus MeSH
- serin-threoninkinasy interagující s receptory metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
B-cell receptor (BCR) is a B cell hallmark surface complex regulating multiple cellular processes in normal as well as malignant B cells. Igα (CD79a)/Igβ (CD79b) are essential components of BCR that are indispensable for its functionality, signal initiation, and signal transduction. CD79a/CD79b-mediated BCR signaling is required for the survival of normal as well as malignant B cells via a wide signaling network. Recent studies identified the great complexity of this signaling network and revealed the emerging role of CD79a/CD79b in signal integration. In this review, we have focused on functional features of CD79a/CD79b, summarized signaling consequences of CD79a/CD79b post-translational modifications, and highlighted specifics of CD79a/CD79b interactions within BCR and related signaling cascades. We have reviewed the complex role of CD79a/CD79b in multiple aspects of normal B cell biology and how is the normal BCR signaling affected by lymphoid neoplasms associated CD79A/CD79B mutations. We have also summarized important unresolved questions and highlighted issues that remain to be explored for better understanding of CD79a/CD79b-mediated signal transduction and the eventual identification of additional therapeutically targetable BCR signaling vulnerabilities.
Nanomedicine is a fast-growing field of nanotechnology. One of the major obstacles for a wider use of nanomaterials for medical application is the lack of standardized toxicity screening protocols for assessing the safety of newly synthesized nanomaterials. In this review, we focus on less frequently studied nanomaterials-induced regulated cell death (RCD) modalities, including eryptosis, necroptosis, pyroptosis, and ferroptosis, as a tool for in vitro nanomaterials safety evaluation. We summarize the latest insights into the mechanisms that mediate these RCDs in response to nanomaterials exposure. Comprehensive data from reviewed studies suggest that ROS (reactive oxygen species) overproduction and ROS-mediated pathways play a central role in nanomaterials-induced RCDs activation. On the other hand, studies also suggest that individual properties of nanomaterials, including size, shape, or surface charge, could determine specific toxicity pathways with consequent RCD induction as well. We anticipate that the evaluation of RCDs can become one of the mechanism-based screening methods in nanotoxicology. In addition to the toxicity assessment, evaluation of necroptosis-, pyroptosis-, and ferroptosis-promoting capacity of nanomaterials could simultaneously provide useful information for specific medical applications as could be their anti-tumor potential. Moreover, a detailed understanding of molecular mechanisms driving nanomaterials-mediated induction of immunogenic RCDs will substantially aid novel anti-tumor nanodrugs development.
- MeSH
- lidé MeSH
- nádory * MeSH
- nanomedicína MeSH
- nanostruktury * toxicita MeSH
- nanotechnologie MeSH
- nekroptóza MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Overall, reactive oxygen species (ROS) signalling significantly contributes to initiation and mo-dulation of multiple regulated cell death (RCD) pathways. Lately, more information has become available about RCD modalities of erythrocytes, including the role of ROS. ROS accumulation has therefore been increasingly recognized as a critical factor involved in eryptosis (apoptosis of erythrocytes) and erythro-necroptosis (necroptosis of erythrocytes). Eryptosis is a Ca2+-dependent apoptosis-like RCD of erythrocytes that occurs in response to oxidative stress, hyperosmolarity, ATP depletion, and a wide range of xenobiotics. Moreover, eryptosis seems to be involved in the pathogenesis of multiple human diseases and pathological processes. Several studies have reported that erythrocytes can also undergo necroptosis, a lytic RIPK1/RIPK3/MLKL-mediated RCD. As an example, erythronecroptosis can occur in response to CD59-specific pore-forming toxins. We have systematically summarized available studies regarding the involvement of ROS and oxidative stress in these two distinct RCDs of erythrocytes. We have focused specifically on cellular signalling pathways involved in ROS-mediated cell death decisions in erythrocytes. Furthermore, we have summarized dysregulation of related erythrocytic antioxidant defence systems. The general concept of the ROS role in eryptotic and necroptotic cell death pathways in erythrocytes seems to be established. However, further studies are required to uncover the complex role of ROS in the crosstalk and interplay between the survival and RCDs of erythrocytes.
- MeSH
- eryptóza * fyziologie MeSH
- erytrocyty metabolismus MeSH
- lidé MeSH
- oxidace-redukce MeSH
- reaktivní formy kyslíku metabolismus MeSH
- vápník metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIM: To evaluate the effects of orally administered gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) on the course of chronic carrageenan-induced intestinal inflammation. METHODS: Samples of small intestinal tissue were collected from four groups of rats (intact, after administration of VNPs, with carrageenaninduced intestinal inflammation, with carrageenan-induced intestinal inflammation orally exposed to VNPs) to assess the intestinal morphology and HSP90α expression. Levels of seromucoid, C-reactive protein, TNF-α, IL-1β and IL-10 were determined in blood serum. RESULTS: Oral exposure to VNPs was associated with neither elevation of inflammation markers in blood serum nor HSP90α overexpression in the small intestine, i.e. no toxic effects of VNPs were observed. Carrageenan-induced intestinal inflammation was accompanied by higher levels of TNF-α and IL-1β, as well as HSP90α upregulation in the intestinal mucosa, compared with controls. Administration of VNPs to rats with enteritis did not lead to statistically significant changes in concentrations of circulating pro-inflammatory cytokines with the trend towards their increase. CONCLUSION: No adverse effects were observed in rats orally exposed to VNPs at a dose of 20 μg/kg during two weeks. Using the experimental model of carrageenan-induced enteritis, it was demonstrated that VNPs at the dose used in our study did not affect the course of intestinal inflammation.
- MeSH
- C-reaktivní protein účinky léků metabolismus MeSH
- enterokolitida krev chemicky indukované patologie MeSH
- gadolinium farmakologie MeSH
- idiopatické střevní záněty krev patologie MeSH
- interleukin-10 krev MeSH
- interleukin-1beta krev účinky léků MeSH
- karagenan toxicita MeSH
- kovové nanočástice * MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- orosomukoid účinky léků metabolismus MeSH
- proteiny tepelného šoku HSP90 účinky léků metabolismus MeSH
- scavengery volných radikálů farmakologie MeSH
- střevní sliznice účinky léků metabolismus patologie MeSH
- TNF-alfa krev účinky léků MeSH
- vanadáty farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
