scholarly journals Current and Emerging Biomarkers of Cell Death in Human Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kongning Li ◽  
Deng Wu ◽  
Xi Chen ◽  
Ting Zhang ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Research Area ◽  
Human Diseases ◽  
Mitotic Catastrophe ◽  
Regulated Necrosis ◽  
Early Diagnose ◽  
Multicellular Organisms ◽  
The Relationship ◽  
Made In

Cell death is a critical biological process, serving many important functions within multicellular organisms. Aberrations in cell death can contribute to the pathology of human diseases. Significant progress made in the research area enormously speeds up our understanding of the biochemical and molecular mechanisms of cell death. According to the distinct morphological and biochemical characteristics, cell death can be triggered by extrinsic or intrinsic apoptosis, regulated necrosis, autophagic cell death, and mitotic catastrophe. Nevertheless, the realization that all of these efforts seek to pursue an effective treatment and cure for the disease has spurred a significant interest in the development of promising biomarkers of cell death to early diagnose disease and accurately predict disease progression and outcome. In this review, we summarize recent knowledge about cell death, survey current and emerging biomarkers of cell death, and discuss the relationship with human diseases.

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Recent Findings of the Types of Programmed Cell Death

2017 ◽  
Vol 5 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Sylwia Borys ◽  
Ronza Khozmi ◽  
Wiesława Kranc ◽  
Artur Bryja ◽  
Marta Dyszkiewicz-Konwińska ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Receptors ◽  
Stress Factors ◽  
Mitotic Catastrophe ◽  
Death Domain ◽  
Apoptotic Pathway ◽  
Response To Stress ◽  
Multicellular Organisms ◽  
Different Characteristics ◽  
Apoptosis And Necrosis

Summary Cell death plays an important role in maintaining the homeostasis of multicellular organisms. It can occur in a controlled manner by apoptosis or autophagy. Cell death which occurs regardless of regulatory factors include necrosis, mitotic catastrophe or oncosis. Apoptosis and necrosis are cellular process that leads to cell death. However their mechanisms are different, although factors triggering them can be similar. Necrosis and apoptosis have many different characteristics in terms of biochemistry and morphology. There are two main pathways of apoptosis induction signal: receptor - dependent and mitochondrial. The outsider apoptotic pathway is induced by external factors stimulating membrane receptors having an intracellular domain called death domain. Mitochondrial apoptotic pathway is activated by increased concentration of reactive oxygen species (ROS), DNA damage, disorders electrolyte transport and an increase in the concentration of the calcium ions in the cytoplasm. In response to stress-factors, mitochondrial channels are opened, so that is released into the cytoplasm cytochrome C. This work is aimed at an overall description of exchanged processes.

The Trafficking Machinery of Lytic and Protein Storage Vacuoles: How Much is Shared and How Much is Distinct?

2021 ◽  
Author(s):  
Xiuxiu Zhang ◽  
Hui Li ◽  
Hai Lu ◽  
Inhwan Hwang
Keyword(s):  
Protein Trafficking ◽  
Molecular Mechanisms ◽  
Protein Storage ◽  
Protein Storage Vacuoles ◽  
Protein Storage Vacuole ◽  
Lytic Vacuoles ◽  
Lytic Vacuole ◽  
The Relationship ◽  
Storage Vacuole ◽  
Made In

Abstract Plant cells contain two types of vacuoles, the lytic vacuole and the protein storage vacuole. Lytic vacuoles (LVs) are present in vegetative cells, whereas protein storage vacuoles (PSVs) are found in seed cells. The physiological functions of the two vacuole types differ. Newly synthesized proteins must be transported to these vacuoles via protein trafficking through the endomembrane system for them to function. Recently, significant advances have been made in elucidating the molecular mechanisms of protein trafficking to these organelles. Despite these advances, the relationship between the trafficking mechanisms in LV and PSVs remains unclear. Some aspects of the trafficking mechanisms are common to both organelles, but certain aspects are specific to trafficking to either LV or PSVs. In this review, we summarize recent findings on the components involved in protein trafficking to both LV and PSVs and compare them to examine the extent of overlap in the trafficking mechanisms. In addition, we discuss the interconnection between the LV and PSVs in protein trafficking machinery and the implication in the identity of these organelles.

scholarly journals Caspase-Independent Regulated Necrosis Pathways as Potential Targets in Cancer Management

2021 ◽  
Vol 10 ◽  
Author(s):  
Jianyao Lou ◽  
Yunxiang Zhou ◽  
Zengyu Feng ◽  
Mindi Ma ◽  
Yihan Yao ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Multiple Modes ◽  
Cancer Management ◽  
Regulated Necrosis ◽  
Anti Cancer ◽  
Cancer Initiation

Regulated necrosis is an emerging type of cell death independent of caspase. Recently, with increasing findings of regulated necrosis in the field of biochemistry and genetics, the underlying molecular mechanisms and signaling pathways of regulated necrosis are gradually understood. Nowadays, there are several modes of regulated necrosis that are tightly related to cancer initiation and development, including necroptosis, ferroptosis, parthanatos, pyroptosis, and so on. What’s more, accumulating evidence shows that various compounds can exhibit the anti-cancer effect via inducing regulated necrosis in cancer cells, which indicates that caspase-independent regulated necrosis pathways are potential targets in cancer management. In this review, we expand the molecular mechanisms as well as signaling pathways of multiple modes of regulated necrosis. We also elaborate on the roles they play in tumorigenesis and discuss how each of the regulated necrosis pathways could be therapeutically targeted.

scholarly journals Targeting Ferroptosis for Lung Diseases: Exploring Novel Strategies in Ferroptosis-Associated Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Tian-Liang Ma ◽  
Yong Zhou ◽  
Ci Wang ◽  
Lu Wang ◽  
Jing-Xian Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Lung Diseases ◽  
Molecular Mechanisms ◽  
Membrane Rupture ◽  
Promising Strategy ◽  
Regulated Cell Death ◽  
Regulated Necrosis ◽  
Organelle Membrane ◽  
Long Chain

Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.

scholarly journals β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances

Metabolites ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 796
Author(s):  
Noyonika Mukherjee ◽  
Li Lin ◽  
Christopher J. Contreras ◽  
Andrew T. Templin
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Cell Loss ◽  
Pathological Process ◽  
Amyloid Formation ◽  
Β Cell ◽  
Islet Amyloid ◽  
Regulated Necrosis ◽  
Islet Inflammation ◽  
Stress Oxidative

β-cell death is regarded as a major event driving loss of insulin secretion and hyperglycemia in both type 1 and type 2 diabetes mellitus. In this review, we explore past, present, and potential future advances in our understanding of the mechanisms that promote β-cell death in diabetes, with a focus on the primary literature. We first review discoveries of insulin insufficiency, β-cell loss, and β-cell death in human diabetes. We discuss findings in humans and mouse models of diabetes related to autoimmune-associated β-cell loss and the roles of autoreactive T cells, B cells, and the β cell itself in this process. We review discoveries of the molecular mechanisms that underlie β-cell death-inducing stimuli, including proinflammatory cytokines, islet amyloid formation, ER stress, oxidative stress, glucotoxicity, and lipotoxicity. Finally, we explore recent perspectives on β-cell death in diabetes, including: (1) the role of the β cell in its own demise, (2) methods and terminology for identifying diverse mechanisms of β-cell death, and (3) whether non-canonical forms of β-cell death, such as regulated necrosis, contribute to islet inflammation and β-cell loss in diabetes. We believe new perspectives on the mechanisms of β-cell death in diabetes will provide a better understanding of this pathological process and may lead to new therapeutic strategies to protect β cells in the setting of diabetes.

scholarly journals Mechanistic paradigms of cell death - revisited

2021 ◽  
Vol 42 (4) ◽  
pp. 903-917
Author(s):  
S.V.S. Rana ◽  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Human Health Risk ◽  
Cell Types ◽  
Enzymatic Antioxidants ◽  
Cellular Targets ◽  
A Cell ◽  
The Impact ◽  
Made In

Present review is the description of a journey that originates from Virchows' cell theory and terminates with the role of molecular switches in cell death recently proposed by Orrenius. Landmark discoveries made, in between, to characterize regulated as well as accidental cell death have also been documented. It embraces the studies that were made in early nineties to understand cellular homeostasis in health and disease. Furthermore, the effects of foreign chemicals on different cell types witnessed in late nineties have been classified into necrosis, apoptosis, autophagy etc. Since it is important to know how a cell dies, studies made in our own and other laboratories on the role of reactive oxygen species, oxidative stress, intracellular Ca2+ homeostasis, redox imbalance, mitochondrial and ER stress in cell death have also been reviewed. Possibility of a cross talk amongst these mechanisms has also been examined. It discusses the impact of wonder molecules like CYP450, GSH, metallothionein and melatonin together with enzymatic and non-enzymatic antioxidants on cell death. Understanding the cellular targets and molecular mechanisms activated by a variety of environmental xenobiotics is fundamental for human health risk assessment. It is expected that the contents of this article will answer the fundamental question- why and how cells die.

Epigenetic drugs for cancer treatment and prevention: mechanisms of action

2010 ◽  
Vol 1 (3-4) ◽  
pp. 239-251 ◽  
Author(s):  
Xiao-Dan Yu ◽  
Z. Sheng Guo
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Mitotic Catastrophe ◽  
Epigenetic Therapy ◽  
Epigenetic Mechanisms ◽  
Epigenetic Drugs ◽  
Treatment And Prevention

AbstractThis review provides a brief overview of the basic principles of epigenetic gene regulation and then focuses on recent development of epigenetic drugs for cancer treatment and prevention with an emphasis on the molecular mechanisms of action. The approved epigenetic drugs are either inhibitors of DNA methyltransferases or histone deacetylases (HDACs). Future epigenetic drugs could include inhibitors for histone methyltransferases and histone demethylases and other epigenetic enzymes. Epigenetic drugs often function in two separate yet interrelated ways. First, as epigenetic drugs per se, they modulate the epigenomes of premalignant and malignant cells to reverse deregulated epigenetic mechanisms, leading to an effective therapeutic strategy (epigenetic therapy). Second, HDACs and other epigenetic enzymes also target non-histone proteins that have regulatory roles in cell proliferation, migration and cell death. Through these processes, these drugs induce cancer cell growth arrest, cell differentiation, inhibition of tumor angiogenesis, or cell death via apoptosis, necrosis, autophagy or mitotic catastrophe (chemotherapy). As they modulate genes which lead to enhanced chemosensitivity, immunogenicity or dampened innate antiviral response of cancer cells, epigenetic drugs often show better efficacy when combined with chemotherapy, immunotherapy or oncolytic virotherapy. In chemoprevention, dietary phytochemicals such as epigallocatechin-3-gallate and sulforaphane act as epigenetic agents and show efficacy by targeting both cancer cells and the tumor microenvironment. Further understanding of how epigenetic mechanisms function in carcinogenesis and cancer progression as well as in normal physiology will enable us to establish a new paradigm for intelligent drug design in the treatment and prevention of cancer.

scholarly journals Current Understanding of the Mechanisms for Clearance of Apoptotic Cells—A Fine Balance

2013 ◽  
Vol 6 ◽  
pp. JCD.S11037 ◽  
Author(s):  
Lois A. Hawkins ◽  
Andrew Devitt
Keyword(s):  
Cell Death ◽  
Innate Immune System ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Apoptotic Cells ◽  
Viable Cells ◽  
Effective Removal ◽  
Multicellular Organisms ◽  
Dying Cells

Apoptosis is an important cell death mechanism by which multicellular organisms remove unwanted cells. It culminates in a rapid, controlled removal of cell corpses by neighboring or recruited viable cells. Whilst many of the molecular mechanisms that mediate corpse clearance are components of the innate immune system, clearance of apoptotic cells is an anti-inflammatory process. Control of cell death is dependent on competing pro-apoptotic and anti-apoptotic signals. Evidence now suggests a similar balance of competing signals is central to the effective removal of cells, through so called ‘eat me’ and ‘don't eat me’ signals. Competing signals are also important for the controlled recruitment of phagocytes to sites of cell death. Consequently recruitment of phagocytes to and from sites of cell death can underlie the resolution or inappropriate propagation of cell death and inflammation. This article highlights our understanding of mechanisms mediating clearance of dying cells and discusses those mechanisms controlling phagocyte migration and how inappropriate control may promote important pathologies.

scholarly journals MO338INCREASED INFLAMMATORY RESPONSE IS A HALLMARK OF AGE-RELATED AGGRAVATION OF EXPERIMENTAL AKI

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Laura Marquez-Exposito ◽  
Lucia Tejedor ◽  
Laura Santos-Sanchez ◽  
Floris A Valentijn ◽  
Elena Cantero-Navarro ◽  
...  
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Cellular Senescence ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Nuclear Staining ◽  
Cell Death Pathway ◽  
Age Related ◽  
Regulated Necrosis ◽  
Young Mice

Abstract Background and Aims Acute kidney injury (AKI) is associated with elevated mortality and morbidity presenting higher frequency in aged patients. Different mechanisms are activated in AKI, including tubular epithelial cell death (apoptosis and regulated necrosis), inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest (or cellular senescence). There is a strong connection between pathways activated in AKI and development of cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular mechanisms in ageing-associated mortality are not completely understood. Our aim was to investigate age-related molecular mechanisms of AKI. Method Experimental nephropathy by folic acid administration (FA, 125mg/kg) was induced in young (3 months) and old (12 months) mice. Renal lesions and mechanisms were evaluated at 48 hours (AKI acute phase). Results AKI mortality was higher in old (50 %) than in young (15%) mice 4 days after FA injection (pilot study). Tubular damage score (PAS evaluation) and KIM-1 tubular expression (renal damage biomarker) were also higher in old than in young FA-injected mice after 48h. The number of infiltrating immune cells (mainly neutrophils and macrophages) and gene expression levels of proinflammatory genes (Lcn-2 and ccl2) were significantly higher in FA kidneys of old as compared to young mice. Regulated necrosis (necroptosis), contrary to apoptosis, induces an inflammatory response and necroinflammation, being macrophages the key effector immune cells of this cell death pathway. Among some of the key necroptosis mediators, MLKL and RIPK3 were higher in old FA kidneys. These data could indicate a magnification of the inflammatory response to AKI in older mice. In contrast, expression of protective factors was dramatically downregulated in old FA mice, including the mitochondrial biogenesis driver PGC-1α, and the antiaging factor Klotho. Cellular senescence was induced in FA kidneys, as indicated by increased levels of cyclin-dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA Damage Response marker yH2AX. Importantly, p21 mRNA expression and nuclear staining for p21 and yH2AX were increased in FA kidneys, and the fold increase was significantly higher in old than in young mice. Also, the expression of senescence-associated secretory phenotype (SASP) components (Tgfb1, Il-6, and Serpine-1) was significantly higher in old FA mouse kidneys. Interestingly, also some infiltrating immune cells were p21/yH2AX positive, suggesting molecular senescence in the immune cells (“immunesenescence”) and inflammation in the ageing kidney (“inflammaging”) are involved in the aggravated AKI response to FA in old mice. Conclusion Our data indicate that in advanced age, exposure to toxic compounds results in a more severe AKI response that might relate to an early inflammatory response characterize by more extensive necroptosis and activation of pathways related to cellular senescence of resident kidney cells and infiltrating inflammatory cells.

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