scholarly journals Conformational states of the cytoprotective protein Bcl-xL

2020 ◽  
Author(s):  
P. Ryzhov ◽  
Y. Tian ◽  
Y. Yao ◽  
A. A. Bobkov ◽  
W. Im ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Md Simulations ◽  
Water Soluble ◽  
Titration Calorimetry ◽  
Intracellular Membranes ◽  
Intrinsically Disordered ◽  
Disordered Loop

ABSTRACTBcl-xL is a major inhibitor of apoptosis, a fundamental homeostatic process of programmed cell death that is highly conserved across evolution. Because it plays prominent roles in cancer, Bcl-xL is a major target for anti-cancer therapy and for studies aimed at understanding its structure and activity. While Bcl-xL is active primarily at intracellular membranes, most studies have focused on soluble forms of the protein lacking both the membrane-anchoring C-terminal tail and the intrinsically disordered loop, and this has resulted in a fragmented view of the protein’s biological activity. Here we describe how these segments affect the protein’s conformation and ligand binding activity in both its soluble and membrane-anchored states. The combined data from nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and isothermal titration calorimetry (ITC) provide information about the molecular basis for the protein’s functionality and a view of its complex molecular mechanisms.SIGNIFICANCEThe human protein Bcl-xL is a key regulator of programmed cell death in health and disease. Structural studies, important for understating the molecular basis for its functions, have advanced primarily by deleting both the long disordered loop that regulates its activity and the C-terminal tail that anchors the protein to intracellular membranes Here we describe the preparation and conformations of full-length Bcl-xL in both its water-soluble and membrane-anchored states. The study provides new biophysical insights about Bcl-xL and its greater Bcl-2 protein family.

scholarly journals Molecular basis of disregulation of programmed lymphocytes’ death in chronic viral infection

2006 ◽  
Vol 5 (2) ◽  
pp. 23-34
Author(s):  
V. V. Novitsky ◽  
N. V. Ryazantseva ◽  
O. B. Zhoukova
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Viral Infection ◽  
Immune Cells ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Recent Literature ◽  
Chronic Viral Infection ◽  
Persistent Viruses

The review analyses information from recent literature and results of the authors’ own investigations concerning imbalance of programmed cell death in forming chronic viral infection. Molecular mechanisms of apoptosis modulation of immune cells by persistent viruses are discussed in the article.

scholarly journals Progress in understanding the role of lncRNA in programmed cell death

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Jiang ◽  
Xiaoyu Zhang ◽  
Xuejun Gu ◽  
Xiaozhuang Li ◽  
Lei Shang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Mechanisms ◽  
Membrane Receptors ◽  
Gene Expressions ◽  
Apoptosis Pathway ◽  
Stem Cell Pluripotency ◽  
Extrinsic Apoptosis ◽  
Related Proteins ◽  
Cycle Regulation

AbstractLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but not translated into proteins. LncRNAs regulate gene expressions at multiple levels, such as chromatin, transcription, and post-transcription. Further, lncRNAs participate in various biological processes such as cell differentiation, cell cycle regulation, and maintenance of stem cell pluripotency. We have previously reported that lncRNAs are closely related to programmed cell death (PCD), which includes apoptosis, autophagy, necroptosis, and ferroptosis. Overexpression of lncRNA can suppress the extrinsic apoptosis pathway by downregulating of membrane receptors and protect tumor cells by inhibiting the expression of necroptosis-related proteins. Some lncRNAs can also act as competitive endogenous RNA to prevent oxidation, thereby inhibiting ferroptosis, while some are known to activate autophagy. The relationship between lncRNA and PCD has promising implications in clinical research, and reports have highlighted this relationship in various cancers such as non-small cell lung cancer and gastric cancer. This review systematically summarizes the advances in the understanding of the molecular mechanisms through which lncRNAs impact PCD.

scholarly journals Mutations in the Parkinson’s Disease-Associated PARK2 Gene Are Accompanied by Imbalance in Programmed Cell Death Systems

Acta Naturae ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 146-149 ◽  
Author(s):  
E. V. Konovalova ◽  
O. M. Lopacheva ◽  
I. A. Grivennikov ◽  
O. S. Lebedeva ◽  
E. В. Dashinimaev ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
Disease Patient ◽  
Parkinsons Disease ◽  
Leading Role ◽  
Midbrain Dopaminergic Neurons ◽  
Induced Pluripotent ◽  
Apoptotic Factors

Parkinsons disease is caused by the degeneration of midbrain dopaminergic neurons. A rare recessive form of the disease may be caused by a mutation in the PARK2 gene, whose product, Parkin, controls mitophagy and programmed cell death. The level of pro- and anti-apoptotic factors of the Bcl-2 family was determined in dopaminergic neurons derived from the induced pluripotent stem cells of a healthy donor and a Parkinsons disease patient bearing PARK2 mutations. Western blotting was used to study the ratios of Bax, Bak, Bcl-2, Bcl-XL, and Bcl-W proteins. The pro-apoptotic Bak protein level in PARK2-neurons was shown to be two times lower than that in healthy cells. In contrast, the expression of the anti-apoptotic factors Bcl-XL, Bcl-W, and Bcl-2 was statistically significantly higher in the mutant cells compared to healthy dopaminergic neurons. These results indicate that PARK2 mutations are accompanied by an imbalance in programmed cell death systems in which non-apoptotic molecular mechanisms play the leading role.

scholarly journals The nitrogen-fixing symbiotic cyanobacterium, Nostoc punctiforme can regulate plant programmed cell death

2020 ◽  
Author(s):  
Samuel P. Belton ◽  
Paul F. McCabe ◽  
Carl K. Y. Ng
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Mechanisms ◽  
Differential Regulation ◽  
Nitrogen Fixing ◽  
Nostoc Punctiforme ◽  
Transcriptional Reprogramming ◽  
Cell Growth And Differentiation ◽  
Transcriptome Resource ◽  
Developmental Signalling

AbstractCyanobacteria such as Nostoc spp. can form nitrogen-fixing symbioses with a broad range of plant species. Unlike other plant-bacteria symbioses, little is understood about the immunological and developmental signalling events induced by Nostoc cyanobionts (symbiotic cyanobacteria). Here, we used suspension cell cultures to elucidate the early molecular mechanisms underpinning the association between cyanobionts and plants by studying the effects of conditioned medium (CM) from Nostoc punctiforme cultures on plant programmed cell death (PCD), a typical immune response activated during incompatible interactions. We showed that N. punctiforme-CM could suppress PCD induced by a temperature stress. Interestingly, this was preceded by significant transcriptional reprogramming, as evidenced by the differential regulation of a network of defence-associated genes, as well as genes implicated in regulating cell growth and differentiation. This work is the first to show that cyanobionts can regulate PCD in plants and provides a valuable transcriptome resource for the early immunological and developmental signalling events elicited by Nostoc cyanobionts.

Programmed Cell Death in Plants: Insights Into developmental and Stress-Induced Cell Death

2021 ◽  
Vol 22 ◽  
Author(s):  
Heba T. Ebeed ◽  
Ahmed A. El-helely
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Plant Development ◽  
Molecular Basis ◽  
Stress Conditions ◽  
Similar Form ◽  
Cellular Homeostasis ◽  
Endogenous Factors ◽  
Selective Elimination

: Programmed cell death (PCD) is a fundamental genetically controlled process in most organisms. PCD is responsible for the selective elimination of damaged or unwanted cells and organs to maintain cellular homeostasis during the organ’s development under normal conditions as well as during defense or adaptation to stressful conditions. PCD pathways have been extensively studied in animals. In plants, studies focusing on understanding the pathways of PCD have advanced significantly. However, the knowledge about the molecular basis of PCD is still very limited. Some PCD pathways that have been discovered in animals are not present in plants or found with a similar form. PCD in plants is developmentally controlled (by endogenous factors) to function in organ development and differentiations as well as environmentally induced (by exogenous stimuli) to help the plant in surviving under stress conditions. Here, we present a review of the role of PCD in plant development and explore different examples of stress-induced PCD as well as highlight the main differences between the plant and animal PCD.

scholarly journals Long-term depression: a cell biological view

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130138 ◽  
Author(s):  
Morgan Sheng ◽  
Ali Ertürk
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dendritic Spines ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Long Term Depression ◽  
A Cell ◽  
Biological Programme

Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.

Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water

1997 ◽  
Vol 16 (9) ◽  
pp. 485-494 ◽  
Author(s):  
Aristo Vojdani ◽  
Eli Mordechai ◽  
Nachman Brautbar
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Level ◽  
Control Group ◽  
Pyrrolidine Dithiocarbamate ◽  
Cycle Progression ◽  
Tertiary Butyl

1 In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce pro grammed cell death. 2 Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene- 5 contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3 Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4 When apoptotic lymphocytes from exposed indivi duals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 ± 1.8 and 12.1 ± 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals ( P<0.0001, Mann-Whitney U-Test). MTBE and ben- a zene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumu lated at the S-G2/M boundaries. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kB). NF-kB was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kB activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kB activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.

scholarly journals Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

2020 ◽  
Vol 21 (19) ◽  
pp. 7279 ◽  
Author(s):  
Ming Yang ◽  
Kwok-Fai So ◽  
Wai Ching Lam ◽  
Amy Cheuk Yin Lo
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Severe Visual Loss ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD’s role as a therapeutic new target for future AMD treatment.

scholarly journals New development of Immune checkpoints blockade in cancer immunotherapy

2019 ◽  
Vol 131 ◽  
pp. 01022
Author(s):  
Feixuan Wu
Keyword(s):  
Cell Death ◽  
Targeted Therapy ◽  
Programmed Cell Death ◽  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Immune Checkpoints ◽  
Main Stream ◽  
Positive Effects

Immunotherapy has become the main stream in cancer treatment nowadays. It includes T cell, NK cell targeted therapy, as well as antibody targeted therapy and its derivatives. Recently immune checkpoints blockade (ICB) has been developed, which are said to be a better method in treatment. The release of negative regulators of immune activation has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte–associated protein 4 (CTLA-4), the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) pathway or the lymphocyte-activated gene-3 (LAG-3) pathway, either alone or in combination. Improvement of treatment benefits from the research in molecular mechanisms of ICB. For example, mechanism of LAG-3 and its valid ligands is unclear, which leads to a misunderstanding that the antibody might be ineffective. After finding these results demonstrating that fibrinogen-like protein 1(FGL1) is an important functional ligand of LAG-3, it reveals the role of this LAG 3-FGL1 pathway in tumor immunity. Although there are some potential side effects, these therapies turn out to have lots of positive effects on most patients. Therefore, this review summarizes the latest advances, hoping that it may have a great contribution to the cancer treatment.

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