scholarly journals Role of Cytosolic 2-Cys Prx1 and Prx2 in Redox Signaling

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 169 ◽  
Author(s):  
Yosup Kim ◽  
Ho Hee Jang
Keyword(s):  
Redox Status ◽  
Redox Signaling ◽  
Amino Acid Sequences ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Interaction Partners ◽  
Catalytic Cysteine ◽  
Cellular Compartments ◽  
Dependent Mechanism

Peroxiredoxins (Prxs), a family of peroxidases, are reactive oxygen species scavengers that hydrolyze H2O2 through catalytic cysteine. Mammalian Prxs comprise six isoforms (typical 2-Cys Prxs; Prx1–4, atypical 2-Cys Prx; Prx5, and 1-Cys Prx; Prx6) that are distributed over various cellular compartments as they are classified according to the position and number of conserved cysteine. 2-Cys Prx1 and Prx2 are abundant proteins that are ubiquitously expressed mainly in the cytosol, and over 90% of their amino acid sequences are homologous. Prx1 and Prx2 protect cells from ROS-mediated oxidative stress through the elimination of H2O2 and regulate cellular signaling through redox-dependent mechanism. In addition, Prx1 and Prx2 are able to bind to a diversity of interaction partners to regulate other various cellular processes in cancer (i.e., regulation of the protein redox status, cell growth, apoptosis, and tumorigenesis). Thus, Prx1 and Prx2 can be potential therapeutic targets and it is particularly important to control their level or activity. This review focuses on cytosolic 2-Cys Prx1 and Prx2 and their role in the regulation of redox signaling based on protein-protein interaction.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

scholarly journals Functional Interactomes of Genes Showing Association with Type-2 Diabetes and Its Intermediate Phenotypic Traits Point towards Adipo-Centric Mechanisms in Its Pathophysiology

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 601
Author(s):  
Aditya Saxena ◽  
Nitin Wahi ◽  
Anshul Kumar ◽  
Sandeep Kumar Mathur
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Network Analysis ◽  
Potential Role ◽  
Phenotypic Traits ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Antidiabetic Treatment

The pathogenic mechanisms causing type 2 diabetes (T2D) are still poorly understood; a greater awareness of its causation can lead to the development of newer and better antidiabetic drugs. In this study, we used a network-based approach to assess the cellular processes associated with protein–protein interaction subnetworks of glycemic traits—HOMA-β and HOMA-IR. Their subnetworks were further analyzed in terms of their overlap with the differentially expressed genes (DEGs) in pancreatic, muscle, and adipose tissue in diabetics. We found several DEGs in these tissues showing an overlap with the HOMA-β subnetwork, suggesting a role of these tissues in β-cell failure. Many genes in the HOMA-IR subnetwork too showed an overlap with the HOMA-β subnetwork. For understanding the functional theme of these subnetworks, a pathway-to-pathway complementary network analysis was done, which identified various adipose biology-related pathways, containing genes involved in both insulin secretion and action. In conclusion, network analysis of genes showing an association between T2D and its intermediate phenotypic traits suggests their potential role in beta cell failure. These genes enriched the adipo-centric pathways and were expressed in both pancreatic and adipose tissue and, therefore, might be one of the potential targets for future antidiabetic treatment.

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 The PACAP-Regulated Gene Selenoprotein T Is Abundantly Expressed in Mouse and Human β-Cells and Its Targeted Inactivation Impairs Glucose Tolerance

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3796-3806 ◽  
Author(s):  
Gaëtan Prevost ◽  
Arnaud Arabo ◽  
Long Jian ◽  
Eddy Quelennec ◽  
Dorthe Cartier ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Redox Status ◽  
Human Islets ◽  
Mutant Mice ◽  
Wild Type ◽  
Β Cells ◽  
Cellular Processes ◽  
Insulin Promoter ◽  
Selenoprotein T

Selenoproteins are involved in the regulation of redox status, which affects several cellular processes, including cell survival and homeostasis. Considerable interest has arisen recently concerning the role of selenoproteins in the regulation of glucose metabolism. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein of the endoplasmic reticulum, is present at high levels in human and mouse pancreas as revealed by immunofluorescence and quantitative PCR. Confocal immunohistochemistry studies revealed that SelT is mostly confined to insulin- and somatostatin-producing cells in mouse and human islets. To elucidate the role of SelT in β-cells, we generated, using a Cre-Lox strategy, a conditional pancreatic β-cell SelT-knockout C57BL/6J mice (SelT-insKO) in which SelT gene disruption is under the control of the rat insulin promoter Cre gene. Glucose administration revealed that male SelT-insKO mice display impaired glucose tolerance. Although insulin sensitivity was not modified in the mutant mice, the ratio of glucose to insulin was significantly higher in the SelT-insKO mice compared with wild-type littermates, pointing to a deficit in insulin production/secretion in mutant mice. In addition, morphometric analysis showed that islets from SelT-insKO mice were smaller and that their number was significantly increased compared with islets from their wild-type littermates. Finally, we found that SelT is up-regulated by pituitary adenylate cyclase-activating polypeptide (PACAP) in β-pancreatic cells and that SelT could act by facilitating a feed-forward mechanism to potentiate insulin secretion induced by the neuropeptide. Our findings are the first to show that the PACAP-regulated SelT is localized in pancreatic β- and δ-cells and is involved in the control of glucose homeostasis.

scholarly journals The Role of BRG1 in Antioxidant and Redox Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Shilong You ◽  
Ying Zhang ◽  
Jiaqi Xu ◽  
Hao Qian ◽  
Shaojun Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chromatin Remodeling ◽  
Redox Homeostasis ◽  
Redox Signaling ◽  
Normal Functioning ◽  
Antioxidant Genes ◽  
Cellular Processes ◽  
Cell Functions ◽  
Chromatin Remodeling Complex

Redox homeostasis is regulated by critical molecules that modulate antioxidant and redox signaling (ARS) within the cell. Imbalances among these molecules can lead to oxidative stress and damage to cell functions, causing a variety of diseases. Brahma-related gene 1 (BRG1), also known as SMARCA4, is the central ATPase catalytic subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, which plays a core role in DNA replication, repair, recombination, and transcriptional regulation. Numerous recent studies show that BRG1 is involved in the regulation of various cellular processes associated with ARS. BRG1, as a major factor in chromatin remodeling, is essential for the repair of oxidative stress-induced DNA damage and the activation of antioxidant genes under oxidative stress. Consequently, a comprehensive understanding of the roles of BRG1 in redox homeostasis is crucial to understand the normal functioning as well as pathological mechanisms. In this review, we summarized and discussed the role of BRG1 in the regulation of ARS.

scholarly journals Presence of an isoform of H+-pyrophosphatase located in the alveolar sacs of a scuticociliate parasite of turbot: physiological consequences

Parasitology ◽  
2016 ◽  
Vol 143 (5) ◽  
pp. 576-587 ◽  
Author(s):  
NATALIA MALLO ◽  
JESÚS LAMAS ◽  
ANA-PAULA DEFELIPE ◽  
MARIA-EUGENIA DECASTRO ◽  
ROSA-ANA SUEIRO ◽  
...  
Keyword(s):  
Amino Acid ◽  
Physiological Role ◽  
Amino Acid Sequences ◽  
Cell Structures ◽  
Gene And Protein Expression ◽  
Conserved Gene ◽  
Eukaryotic Organisms ◽  
Cellular Compartments ◽  
First Time

SUMMARYH+-pyrophosphatases (H+-PPases) are integral membrane proteins that couple pyrophosphate energy to an electrochemical gradient across biological membranes and promote the acidification of cellular compartments. Eukaryotic organisms, essentially plants and protozoan parasites, contain various types of H+-PPases associated with vacuoles, plasma membrane and acidic Ca+2storage organelles called acidocalcisomes. We used Lysotracker Red DND-99 staining to identify two acidic cellular compartments in trophozoites of the marine scuticociliate parasitePhilasterides dicentrarchi: the phagocytic vacuoles and the alveolar sacs. The membranes of these compartments also contain H+-PPase, which may promote acidification of these cell structures. We also demonstrated for the first time that theP. dicentrarchiH+-PPase has two isoforms: H+-PPase 1 and 2. Isoform 2, which is probably generated by splicing, is located in the membranes of the alveolar sacs and has an amino acid motif recognized by the H+-PPase-specific antibody PABHK. The amino acid sequences of different isolates of this ciliate are highly conserved. Gene and protein expression in this isoform are significantly regulated by variations in salinity, indicating a possible physiological role of this enzyme and the alveolar sacs in osmoregulation and salt tolerance inP. dicentrarchi.

NH2 terminus of serum and glucocorticoid-regulated kinase 1 binds to phosphoinositides and is essential for isoform-specific physiological functions

2007 ◽  
Vol 292 (6) ◽  
pp. F1741-F1750 ◽  
Author(s):  
Alan C. Pao ◽  
James A. McCormick ◽  
Hongyan Li ◽  
John Siu ◽  
Cedric Govaerts ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kinase Activity ◽  
Regulatory Protein ◽  
Forkhead Transcription Factor ◽  
Cellular Processes ◽  
Cellular Compartments ◽  
Stimulation Of

Serum and glucocorticoid regulated kinase 1 (SGK1) has been identified as a key regulatory protein that controls a diverse set of cellular processes including sodium (Na+) homeostasis, osmoregulation, cell survival, and cell proliferation. Two other SGK isoforms, SGK2 and SGK3, have been identified, which differ most markedly from SGK1 in their NH2-terminal domains. We found that SGK1 and SGK3 are potent stimulators of epithelial Na+ channel (ENaC)-dependent Na+ transport, while SGK2, which has a short NH2 terminus, is a weak stimulator of ENaC. Further characterization of the role of the SGK1 NH2 terminus revealed that its deletion does not affect in vitro kinase activity but profoundly limits the ability of SGK1 either to stimulate ENaC-dependent Na+ transport or inhibit Forkhead-dependent gene transcription. The NH2 terminus of SGK1, which shares sequence homology with the phosphoinositide 3-phosphate [PI( 3 )P] binding domain of SGK3, binds phosphoinositides in protein lipid overlay assays, interacting specifically with PI( 3 )P, PI( 4 )P, and PI( 5 )P, but not with PI( 3 , 4 , 5 )P3. Moreover, a point mutation that reduces phosphoinositide binding to the NH2 terminus also reduces SGK1 effects on Na+ transport and Forkhead activity. These data suggest that the NH2 terminus, although not required for PI 3-kinase-dependent modulation of SGK1 catalytic activity, is required for multiple SGK1 functions, including stimulation of ENaC and inhibition of the proapoptotic Forkhead transcription factor. Together, these observations support the idea that the NH2-terminal domain acts downstream of PI 3-kinase-dependent activation to target the kinase to specific cellular compartments and/or substrates, possibly through its interactions with a subset of phosphoinositides.

scholarly journals The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1055 ◽  
Author(s):  
Yang ◽  
Wu ◽  
Yen ◽  
Liu ◽  
Hwang ◽  
...  
Keyword(s):  
Drug Target ◽  
Redox Homeostasis ◽  
Redox Signaling ◽  
G6pd Activity ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Cellular Processes ◽  
Reducing Equivalent ◽  
Glucose 6 Phosphate Dehydrogenase

The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.

scholarly journals Regulation of Glucose Metabolism by NAD+ and ADP-Ribosylation

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 890 ◽  
Author(s):  
Hopp ◽  
Grüter ◽  
Hottiger
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Pathways ◽  
Redox Reactions ◽  
Genotoxic Stress ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
Energy Needs ◽  
Cellular Compartments

Cells constantly adapt their metabolic pathways to meet their energy needs and respond to nutrient availability. During the last two decades, it has become increasingly clear that NAD+, a coenzyme in redox reactions, also mediates several ubiquitous cell signaling processes. Protein ADP-ribosylation is a post-translational modification that uses NAD+ as a substrate and is best known as part of the genotoxic stress response. However, there is increasing evidence that NAD+-dependent ADP-ribosylation regulates other cellular processes, including metabolic pathways. In this review, we will describe the compartmentalized regulation of NAD+ biosynthesis, consumption, and regeneration with a particular focus on the role of ADP-ribosylation in the regulation of glucose metabolism in different cellular compartments.

scholarly journals Unbalanced Sphingolipid Metabolism and Its Implications for the Pathogenesis of Psoriasis

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1130 ◽  
Author(s):  
Katarzyna Bocheńska ◽  
Magdalena Gabig-Cimińska
Keyword(s):  
Skin Barrier ◽  
Immune Dysregulation ◽  
Sphingolipid Metabolism ◽  
Complex Interplay ◽  
Signalling Molecules ◽  
Cellular Processes ◽  
Immune Mediated ◽  
Diseased Skin ◽  
Cellular Compartments

Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), intricately characterized by perturbations in these cellular processes, are associated with altered composition and unbalanced metabolism of epidermal SLs, more education to precisely determine the role of SLs, especially in the pathogenesis of skin disorders, is needed. PsO is caused by a complex interplay between skin barrier disruption, immune dysregulation, host genetics and environmental triggers. The contribution of particular cellular compartments and organelles in SL metabolism, a process related to dysfunction of lysosomes in PsO, seems to have a significant impact on lysosomal signalling linked to a modulation of the immune-mediated inflammation accompanying this dermatosis and is not fully understood. It is also worth noting that a prominent skin disorder, such as PsO, has diminished levels of the main epidermal SL ceramide (Cer), reflecting altered SL metabolism, that may contribute not only to pathogenesis but also to disease severity and/or progression. This review provides a brief synopsis of the implications of SLs in PsO, aims to elucidate the roles of these molecules in complex cellular processes deregulated in diseased skin tissue and highlights the need for increased research in the field. The significance of SLs as structural and signalling molecules and their actions in inflammation, in which these components are factors responsible for vascular endothelium abnormalities in the development of PsO, are discussed.

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