scholarly journals Reactive oxygen species-independent activation of the IL-1  inflammasome in cells from patients with chronic granulomatous disease

2010 ◽  
Vol 107 (7) ◽  
pp. 3030-3033 ◽  
Author(s):  
F. L. van de Veerdonk ◽  
S. P. Smeekens ◽  
L. A. B. Joosten ◽  
B. J. Kullberg ◽  
C. A. Dinarello ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Granulomatous Disease ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Granulomatous Disease ◽  
In Cells

EROS is required for phagocyte NADPH oxidase function in humans and its deficiency causes Chronic Granulomatous Disease

2018 ◽  
Author(s):  
David C. Thomas ◽  
Louis-Marie Charbonnier ◽  
Andrea Schejtman ◽  
Hasan Aldhekri ◽  
Eve Coomber ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Respiratory Burst ◽  
Reactive Oxygen ◽  
Human Cells ◽  
List Type ◽  
Oxygen Species ◽  
Granulomatous Disease ◽  
Phagocyte Nadph Oxidase

AbstractThe phagocyte respiratory burst is mediated by the phagocyte NADPH oxidase, a multi-protein subunit complex that facilitates production of reactive oxygen species and which is essential for host defence. Monogenic deficiency of individual subunits leads to chronic granulomatous disease (CGD), which is characterized by an inability to make reactive oxygen species, leading to severe opportunistic infections and auto-inflammation. However, not all cases of CGD are due to mutations in previously identified subunits. We recently showed that Eros, a novel and highly conserved ER-resident transmembrane protein, is essential for the phagocyte respiratory burst in mice because it is required for expression of gp91phox-p22phox heterodimer, which are the membrane bound components of the phagocyte NADPH oxidase. We now show that the function of EROS is conserved in human cells and describe a case of CGD secondary to a homozygous EROS mutation that abolishes EROS protein expression. This work demonstrates the fundamental importance of EROS in human immunity and describes a novel cause of CGD.Clinical ImplicationsChronic granulomatous disease is caused by an inability to make reactive oxygen species via the phagocyte NADPH oxidase. Mutations in C17ORF62/EROS, which controls gp91phox- p22phox abundance, are a novel cause of chronic granulomatous disease.Key MessagesThe murine gene, Eros, is known to regulate abundance of gp91phox-p22phox heterodimer and Eros deficient mice are susceptible to infectionWe show that the function of EROS is conserved in human cells and that a homozygous mutation in EROS causes chronic granulomatous disease

Abstract 097: Recombinant Human Erythropoietin Prevents Reactive Oxygen Species - Induced Apoptosis Via Akt and p38 MAPK Pathway During Hypoxia/ Reperfusion Injury

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Asiya Parvin Allaudeen ◽  
Ajay Devendran ◽  
John E Baker ◽  
Anuradha Dhanasekaran
Keyword(s):  
Reactive Oxygen Species ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
Intact Cell ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Oxygen Species ◽  
Human Erythropoietin ◽  
In Cells

Erythropoietin (EPO) is a cytokine produced primarily in the kidney that is essential for red blood cell production. Apart from playing a role in hematopoiesis, EPO also has a protective role in heart myocytes, ovarian, glial cells brain and retinal diseases. In this study we observed that recombinant human EPO (rhEPO) reduces Hypoxia/ Reperfusion (H/R) injury by virtue of its effect on EPO receptor prosurvival signaling pathway, which ultimately leads to reduced expression of apoptotic proteins and increased survival of cardiomyocytes. H9C2 cells were exposed to H/R with or without pretreatment using 10, 15 and 20 U/ml of rhEPO. We determined viability using MTT, nuclear fragmentation by Hoechst staining, apoptotic nuclei by Acridine orange and Ethidium bromide, Reactive Oxygen Species (ROS) by Dicholorofluoresin Diacetate and activity of late apoptotic protease, Caspase-3 by colorimetric Caspase-3 assay. The expression of mitochondrial superoxide dismutase (MnSOD) by RT-PCR and Western blot, phospho-Akt and p38 MAPK by Confocal microscopy were analyzed. Cell viability is increased in cells pretreated with rhEPO compared to cell exposed to H/R. Cells subjected to H/R showed early apoptotic and late apoptotic cells but showed normal nuclei with intact cell membrane in cells pretreated with rhEPO. Intracellular production of ROS and Caspase-3 activity was decreased in cells pretreated with rhEPO compared to cells exposed to H/R. The expression of MnSOD RNA and protein was up-regulated in response to rhEPO, but not in H/R. The phosphorylative activation of Akt, p38MAPK progressively diminished during H/R but increased in rhEPO pretreated cells. We show that rhEPO prevents apoptosis in cardiomyocytes, subjected to H/R injury via phosphorylation of Akt and p38MAPK. These results it is hoped would help us distinguish the cell signaling pathways involved in cardioprotection and thus would open new avenues in cardiovascular therapy.

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