Molecular Pathways of Different Types of Cell Death: Many Roads to Death

2009 ◽  
pp. 3-31 ◽  
Author(s):  
Dmitri V. Krysko ◽  
Agnieszka Kaczmarek ◽  
Peter Vandenabeele
Keyword(s):  
Cell Death ◽  
Molecular Pathways ◽  
Different Types

scholarly journals A link between mitotic defects and mitotic catastrophe: detection and cell fate

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Elena V. Sazonova ◽  
Svetlana V. Petrichuk ◽  
Gelina S. Kopeina ◽  
Boris Zhivotovsky
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Clinical Practice ◽  
Cell Fate ◽  
Mitotic Catastrophe ◽  
Cell Aging ◽  
Molecular Pathways ◽  
Cycle Arrest ◽  
Different Types

AbstractAlthough the phenomenon of mitotic catastrophe was first described more than 80 years ago, only recently has this term been used to explain a mechanism of cell death linked to delayed mitosis. Several mechanisms have been suggested for mitotic catastrophe development and cell fate. Depending on molecular perturbations, mitotic catastrophe can end in three types of cell death, namely apoptosis, necrosis, or autophagy. Moreover, mitotic catastrophe can be associated with different types of cell aging, the development of which negatively affects tumor elimination and, consequently, reduces the therapeutic effect. The effective triggering of mitotic catastrophe in clinical practice requires induction of DNA damage as well as inhibition of the molecular pathways that regulate cell cycle arrest and DNA repair. Here we discuss various methods to detect mitotic catastrophe, the mechanisms of its development, and the attempts to use this phenomenon in cancer treatment.

Quercetin in attenuation of ischemic/reperfusion injury: A review

2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Blood Supply ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Cell Membrane Integrity ◽  
Cell Membrane Disruption

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

scholarly journals The Crosstalk Between Long Non-Coding RNAs and Various Types of Death in Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Wenwen Tang ◽  
Shaomi Zhu ◽  
Xin Liang ◽  
Chi Liu ◽  
Linjiang Song
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Causes Of Death ◽  
Vital Role ◽  
Cancer Cell Proliferation ◽  
Biological Targets ◽  
Cancer Cell Death ◽  
Different Types ◽  
Non Coding Rnas ◽  
Tumor Death

With the increasing aging population, cancer has become one of the leading causes of death worldwide, and the number of cancer cases and deaths is only anticipated to grow further. Long non-coding RNAs (lncRNAs), which are closely associated with the expression level of downstream genes and various types of bioactivity, are regarded as one of the key regulators of cancer cell proliferation and death. Cell death, including apoptosis, necrosis, autophagy, pyroptosis, and ferroptosis, plays a vital role in the progression of cancer. A better understanding of the regulatory relationships between lncRNAs and these various types of cancer cell death is therefore urgently required. The occurrence and development of tumors can be controlled by increasing or decreasing the expression of lncRNAs, a method which confers broad prospects for cancer treatment. Therefore, it is urgent for us to understand the influence of lncRNAs on the development of different modes of tumor death, and to evaluate whether lncRNAs have the potential to be used as biological targets for inducing cell death and predicting prognosis and recurrence of chemotherapy. The purpose of this review is to provide an overview of the various forms of cancer cell death, including apoptosis, necrosis, autophagy, pyroptosis, and ferroptosis, and to describe the mechanisms of different types of cancer cell death that are regulated by lncRNAs in order to explore potential targets for cancer therapy.

scholarly journals Death Receptor-Induced Activation of Initiator Caspase 8 Is Antagonized by Serine/Threonine Kinase PAK4

2003 ◽  
Vol 23 (21) ◽  
pp. 7838-7848 ◽  
Author(s):  
Nerina Gnesutta ◽  
Audrey Minden
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Intracellular Signaling ◽  
Death Receptor ◽  
Caspase 8 ◽  
Death Domain ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Different Types ◽  
Promote Cell Survival

ABSTRACT Normal cell growth requires a precisely controlled balance between cell death and survival. This involves activation of different types of intracellular signaling cascades within the cell. While some types of signaling proteins regulate apoptosis, or programmed cell death, other proteins within the cell can promote survival. The serine/threonine kinase PAK4 can protect cells from apoptosis in response to several different types of stimuli. As is the case for other members of the p21-activated kinase (PAK) family, one way that PAK4 may promote cell survival is by phosphorylating and thereby inhibiting the proapoptotic protein Bad. This leads in turn to the inhibition of effector caspases such as caspase 3. Here we show that in response to cytokines which activate death domain-containing receptors, such as the tumor necrosis factor and Fas receptors, PAK4 can inhibit the death signal by a different mechanism. Under these conditions, PAK4 inhibits apoptosis early in the caspase cascade, antagonizing the activation of initiator caspase 8. This inhibition, which does not require PAK4's kinase activity, may involve inhibition of caspase 8 recruitment to the death domain receptors. This role in regulating initiator caspases is an entirely novel role for the PAK proteins and suggests a new mechanism by which these proteins promote cell survival.

scholarly journals The evolution of regulated cell death pathways in animals and their evasion by pathogens

2022 ◽  
Vol 102 (1) ◽  
pp. 411-454
Author(s):  
Bart Tummers ◽  
Douglas R. Green
Keyword(s):  
Cell Death ◽  
Physiological Traits ◽  
Molecular Pathways ◽  
Host Pathogen Interactions ◽  
Cell Death Pathways ◽  
Regulated Cell Death ◽  
Host Pathogen ◽  
Animal Hosts

The coevolution of host-pathogen interactions underlies many human physiological traits associated with protection from or susceptibility to infections. Among the mechanisms that animals utilize to control infections are the regulated cell death pathways of pyroptosis, apoptosis, and necroptosis. Over the course of evolution these pathways have become intricate and complex, coevolving with microbes that infect animal hosts. Microbes, in turn, have evolved strategies to interfere with the pathways of regulated cell death to avoid eradication by the host. Here, we present an overview of the mechanisms of regulated cell death in Animalia and the strategies devised by pathogens to interfere with these processes. We review the molecular pathways of regulated cell death, their roles in infection, and how they are perturbed by viruses and bacteria, providing insights into the coevolution of host-pathogen interactions and cell death pathways.

scholarly journals Indirubin and Indirubin Derivatives for Counteracting Proliferative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Tina Blažević ◽  
Elke H. Heiss ◽  
Atanas G. Atanasov ◽  
Johannes M. Breuss ◽  
Verena M. Dirsch ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Active Component ◽  
Clinical Results ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Pharmacokinetic Properties ◽  
Different Types ◽  
Traditional Chinese Medicine Formulation ◽  
Made In

Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. The encouraging clinical results from the 1980s obtained in chronic myelocytic leukemia patients treated with indirubin stimulated numerous studies on this compound. These investigations explored the use of indirubin in different types of cancer and reported the synthesis of novel derivatives with improved chemical and pharmacokinetic properties. In this paper, we review the impressive progress that has been made in elucidating the mechanistic understanding of how indirubin and its derivatives affect physiological and pathophysiological processes, mainly by inhibition of cell proliferation and induction of cell death. Furthermore, we survey the therapeutic use of these compounds in combating proliferative diseases such as cancer, restenosis, and psoriasis.

scholarly journals Visualizing Cell Death in Experimental Focal Cerebral Ischemia: Promises, Problems, and Perspectives

2011 ◽  
Vol 32 (2) ◽  
pp. 213-231 ◽  
Author(s):  
Marietta Zille ◽  
Tracy D Farr ◽  
Ingo Przesdzing ◽  
Jochen Müller ◽  
Clemens Sommer ◽  
...  
Keyword(s):  
Cell Death ◽  
Complex Disease ◽  
Focal Cerebral Ischemia ◽  
Cell Damage ◽  
Brain Cells ◽  
Pathological Features ◽  
Advantages And Disadvantages ◽  
Different Types ◽  
Immunohistochemical Techniques ◽  
Eventual Death

One of the hallmarks of stroke pathophysiology is the widespread death of many different types of brain cells. As our understanding of the complex disease that is stroke has grown, it is now generally accepted that various different mechanisms can result in cell damage and eventual death. A plethora of techniques is available to identify various pathological features of cell death in stroke; each has its own drawbacks and pitfalls, and most are unable to distinguish between different types of cell death, which partially explains the widespread misuse of many terms. The purpose of this review is to summarize the standard histopathological and immunohistochemical techniques used to identify various pathological features of stroke. We then discuss how these methods should be properly interpreted on the basis of what they are showing, as well as advantages and disadvantages that require consideration. As there is much interest in the visualization of stroke using noninvasive imaging strategies, we also specifically discuss how these techniques can be interpreted within the context of cell death.

BCL6 Programs Lymphoma Cells for Survival and Differentiation through Distinct Biochemical Mechanisms, Both of Which Can Be Therapeutically Targeted.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 225-225 ◽  
Author(s):  
Samir Parekh ◽  
Jose Polo ◽  
Przemyslaw Juszczynski ◽  
Paola Lev ◽  
Stella Ranuncolo ◽  
...  
Keyword(s):  
Cell Death ◽  
Target Genes ◽  
Constitutive Expression ◽  
Lymphoma Cells ◽  
Proliferation And Differentiation ◽  
Different Types ◽  
Biochemical Mechanisms ◽  
Highly Correlated ◽  
On Chip ◽  
Specific Peptide

Abstract The BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCL). Constitutive expression of BCL6 has been proposed to mediate lymphomagenesis through several mechanisms, including evasion of cell death, proliferation and differentiation blockade. We show here that BCL6 mediates these effects through distinct mechanisms. First, we show that blocking the association of the SMRT corepressor with BCL6 using our specific peptide inhibitor (BPI) abrogates only the survival effects of BCL6 but has no effect on differentiation. Accordingly, BPI upregulates survival genes such as ATR and p53, but not genes associated with differentiation such as Blimp1, XBP and Syndecan. In contrast, BCL6 shRNA upregulates both survival and differentiation genes and induces both cell death and differentiation. We and others have shown that BCL6 can also directly bind to the MTA3 corepressor, which is implicated in differentiation of Burkitt lymphoma cells. We found that BCL6 and MTA3 are co-expressed in DLBCL cells and primary human centroblasts (the precursor cell for most DLBCLs). The endogenous BCL6 and MTA3 proteins interacted in DLBCLs cells in co-immunoprecipitation experiments. In contrast to SMRT blockade with BPI, siRNA depletion of MTA3 induced expression of the Blimp1, XBP and Syndecan but not p53 and ATR. MTA3 depletion induced plasmacytic differentiation within 72 hours as shown in functional assays and by surface markers. We performed ChIP on chip using custom arrays densely tiling with oligonucleotides covering the entire genomic loci of 20 BCL6 target genes. Interestingly, BCL6 formed different types of repression complexes at differentiation genes (Complex with MTA3/NuRD) vs. survival genes (complex with SMRT and N-CoR). BCL6-mediated repression of genes involved in survival and differentiation thus depend on distinct biochemical mechanisms. The relevance of these findings for human disease was underscored by the fact that we found a statistically significant positive correlation between MTA3 and BCL6 gene expression in a database of 176 human DLBCLs (p<0.00001). Likewise, protein expression of BCL6 and MTA3 was also highly correlated (p<0.00001) (74 cases examined) and staining for Blimp1 revealed mutually exclusive expression from MTA3. Taken together these results illustrate the basic mechanisms through which BCL6 mediates DLBCL lymphomagenesis and provide the basis for powerful targeted therapy regimens that could be translated to the clinical setting.

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