The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction

2006 ◽  
Vol 111 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Mark T. Quinn ◽  
Mary Cloud B. Ammons ◽  
Frank R. DeLeo
Keyword(s):  
Nadph Oxidase ◽  
The Body ◽  
Host Defence ◽  
Nadph Oxidases ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Health And Disease ◽  
Micro Organisms ◽  
Produce Superoxide Anion

The NADPH oxidase was originally identified as a key component of human innate host defence. In phagocytes, this enzyme complex is activated to produce superoxide anion and other secondarily derived ROS (reactive oxygen species), which promote killing of invading micro-organisms. However, it is now well-established that NADPH oxidase and related enzymes also participate in important cellular processes not directly related to host defence, including signal transduction, cell proliferation and apoptosis. These enzymes are present in essentially every organ system in the body and contribute to a multitude of physiological events. Although essential for human health, excess NADPH-oxidase-generated ROS can promote numerous pathological conditions. Herein, we summarize our current understanding of NADPH oxidases and provide an overview of how they contribute to specific human diseases.

Integrative view of serpins in health and disease: the contribution of serpinA3

2020 ◽  
Author(s):  
Andrea Sanchez-Navarro ◽  
Isaac González-Soria ◽  
Rebecca Caldiño-Bohn ◽  
Norma A. Bobadilla
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cellular Processes ◽  
Hormone Transport ◽  
Integrative View ◽  
Health And Disease ◽  
The Brain ◽  
Regulation Of Blood Pressure ◽  
Common Function

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular, and kidney disorders are intensively studied to find effective therapeutic targets. Given serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin have been associated with diverse pathophysiological events. In particular, we will focus on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes, as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.

scholarly journals A control engineering approach to understanding the TGF-β paradox in cancer

2011 ◽  
Vol 9 (71) ◽  
pp. 1389-1397 ◽  
Author(s):  
Seung-Wook Chung ◽  
Carlton R. Cooper ◽  
Mary C. Farach-Carson ◽  
Babatunde A. Ogunnaike
Keyword(s):  
Cancer Cells ◽  
Mechanistic Model ◽  
Tumour Suppressor ◽  
Cancer Tissue ◽  
Control Engineering ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
High Level ◽  
Quantitative Explanation

TGF-β, a key cytokine that regulates diverse cellular processes, including proliferation and apoptosis, appears to function paradoxically as a tumour suppressor in normal cells, and as a tumour promoter in cancer cells, but the mechanisms underlying such contradictory roles remain unknown. In particular, given that this cytokine is primarily a tumour suppressor, the conundrum of the unusually high level of TGF-β observed in the primary cancer tissue and blood samples of cancer patients with the worst prognosis, remains unresolved. To provide a quantitative explanation of these paradoxical observations, we present, from a control theory perspective, a mechanistic model of TGF-β-driven regulation of cell homeostasis. Analysis of the overall system model yields quantitative insight into how cell population is regulated, enabling us to propose a plausible explanation for the paradox: with the tumour suppressor role of TGF-β unchanged from normal to cancer cells, we demonstrate that the observed increased level of TGF-β is an effect of cancer cell phenotypic progression (specifically, acquired TGF-β resistance), not the cause . We are thus able to explain precisely why the clinically observed correlation between elevated TGF-β levels and poor prognosis is in fact consistent with TGF-β's original (and unchanged) role as a tumour suppressor.

Pathogenesis as a problem of functional incompetence and imbalance in the population of T-lymphocytes

2021 ◽  
pp. 109-119
Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская
Keyword(s):  
T Lymphocytes ◽  
Personalized Medicine ◽  
The Body ◽  
Lymphoid Cells ◽  
Human Diseases ◽  
Regulatory Role ◽  
Total Rna ◽  
Physiological Processes ◽  
Health And Disease

Цель обзора - анализ клеточной основы патогенеза различных заболеваний в свете регуляторной роли Т-лимфоцитов. Рассматривается роль поликлонального многообразия популяции Т-лимфоцитов, особых свойств этих клеток-представителей гомеостатической системы организма в физиологических процессах в норме и при патологии. Указаны перспективы терапевтического и профилактического воздействий, связанные с использованием суммарных РНК нормальных лимфоидных клеток аллогенной и ксеногенной природы. Указана также возможность создания с помощью лимфоцитарных суммарных РНК адекватных моделей заболеваний человека на пути к развитию персонифицированной медицины. This review provides an analysis of the cellular basis of the pathogenesis of various diseases in the light of the regulatory role of T-lymphocytes. The role of the polyclonal diversity of the population of T-lymphocytes, the special properties of these cells-representatives of the homeostatic system of the body, in physiological processes in health and disease is considered. Prospects for therapeutic and prophylactic effects associated with the use of total RNA of normal lymphoid cells of allogeneic and xenogenic origin are indicated. The possibility of creating, using lymphocytic total RNA, adequate models of human diseases for the development of personalized medicine is also indicated.

Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

2011 ◽  
Vol 439 (3) ◽  
pp. 349-378 ◽  
Author(s):  
Anthony J. Morgan ◽  
Frances M. Platt ◽  
Emyr Lloyd-Evans ◽  
Antony Galione
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Late Endosomes ◽  
Wide Range ◽  
Health And Disease ◽  
Lysosome Related Organelles ◽  
Cellular Compartments ◽  
Endosomal Vesicles ◽  
Intracellular Targets

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

scholarly journals Role of Glutathione in Cancer Progression and Chemoresistance

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nicola Traverso ◽  
Roberta Ricciarelli ◽  
Mariapaola Nitti ◽  
Barbara Marengo ◽  
Anna Lisa Furfaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Cytotoxic Effects ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Glutathione Disulphide ◽  
Increased Susceptibility

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents.

scholarly journals Emerging impact of the long noncoding RNA MIR22HG on proliferation and apoptosis in multiple human cancers

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Le Zhang ◽  
Cuixia Li ◽  
Xiulan Su
Keyword(s):  
Chromatin Remodeling ◽  
Noncoding Rna ◽  
Potential Role ◽  
Immune Escape ◽  
Prognostic Biomarker ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Underlying Mechanisms ◽  
Competitive Endogenous Rna

AbstractAn increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in diverse cellular processes, including proliferation, apoptosis, migration, invasion, chromatin remodeling, metabolism and immune escape. Clinically, the expression of MIR22HG is increased in many human tumors (colorectal cancer, gastric cancer, hepatocellular carcinoma, lung cancer, and thyroid carcinoma), while in others (esophageal adenocarcinoma and glioblastoma), it is significantly decreased. Moreover, MIR22HG has been reported to function as a competitive endogenous RNA (ceRNA), be involved in signaling pathways, interact with proteins and interplay with miRNAs as a host gene to participate in tumorigenesis and tumor progression. In this review, we describe the biological functions of MIR22HG, reveal its underlying mechanisms for cancer regulation, and highlight the potential role of MIR22HG as a novel cancer prognostic biomarker and therapeutic target that can increase the efficacy of immunotherapy and targeted therapy for cancer treatment.

scholarly journals Probiotics and Periodontal Disease: A Current Update

2010 ◽  
Vol 4 (Spl) ◽  
pp. 35-37
Author(s):  
Vivek Gupta ◽  
Bhavana Gupta
Keyword(s):  
Oral Health ◽  
Periodontal Disease ◽  
Present Article ◽  
Periodontal Health ◽  
Health And Disease ◽  
Systemic Health ◽  
Micro Organisms ◽  
The Impact ◽  
A Current

ABSTRACT Probiotics are live micro-organisms that when administered in adequate amounts confer health benefits upon the host. Although a lot of work has been done regarding the effects of probiotic applications on systemic health particularly gastro-intestinal, the impact of probiotics on oral health is relatively new with lots of research going on; the area of probiotics and periodontal disease is still in its infancy. The present article summarizes the role of probiotics in periodontal health and disease and its effectiveness in periodontal therapy.

scholarly journals Going Beyond Bacteria: Uncovering the Role of Archaeome and Mycobiome in Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yashar Houshyar ◽  
Luca Massimino ◽  
Luigi Antonio Lamparelli ◽  
Silvio Danese ◽  
Federica Ungaro
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
The Body ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Therefore, the full understanding of the archaeome and mycobiome dysbiosis during IBD pathogenesis may pave the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.

scholarly journals Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections

2021 ◽  
Author(s):  
Paulina Niedźwiedzka-Rystwej ◽  
Dominika Bębnowska ◽  
Roman Kołacz ◽  
Wiesław Deptuła
Keyword(s):  
Pattern Recognition ◽  
Viral Infections ◽  
Apoptotic Cell ◽  
Pattern Recognition Receptors ◽  
The Body ◽  
The Other ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Other Hand

Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.

scholarly journals Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease

2017 ◽  
Vol 131 (15) ◽  
pp. 1919-1922 ◽  
Author(s):  
Gareth A. Nye ◽  
Giorgos K. Sakellariou ◽  
Hans Degens ◽  
Adam P. Lightfoot
Keyword(s):  
Skeletal Muscle ◽  
Sexual Dimorphism ◽  
Mitochondrial Function ◽  
Recent Article ◽  
Cellular Processes ◽  
Wide Range ◽  
Health And Disease ◽  
Muscle Health ◽  
The Impact

Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies. However, the impact of sexual dimorphism in this context is less clear, with several studies reporting conflicting observations. For instance in ageing studies, a rodent model reported female muscles have higher antioxidant capacity compared with males; in contrast, human studies demonstrate no sex difference in mitochondrial bioenergetics and oxidative damage. These divergent observations highlight the importance of considering models and methods used to examine mitochondrial function, when interpreting these data. The use of either isolated or intact mitochondrial preparations in many studies appears likely to be a source of discord, when comparing many studies. Overall, it is now clear that more research is needed to determine if sexual dimorphism is a contributing factor in the development of myopathologies.

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