WldS ameliorates renal injury in a type 1 diabetic mouse model

2014 ◽  
Vol 306 (11) ◽  
pp. F1348-F1356 ◽  
Author(s):  
Shuaishuai Zhu ◽  
Yelin Yang ◽  
Jin Hu ◽  
Lingling Qian ◽  
Yuchen Jiang ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Early Stage ◽  
Periodic Acid ◽  
Diabetic Mouse ◽  
Erk Signaling ◽  
Periodic Acid Schiff ◽  
Nadph Oxidase Activity ◽  
Tnf Α ◽  
Nadh Ratio

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. The purpose of this study is to investigate whether the WldS (slow Wallerian degeneration; also known as Wld) gene plays a renoprotective role during the progression of DN. Diabetes was induced in 8-wk-old male wild-type (WT) and C57BL/WldS mice by streptozotocin (STZ) injection. Blood and urinary variables including blood glucose, glycated hemoglobin (GHb), insulin, urea nitrogen, and albumin/creatinine ratio were assessed 4, 7, and 14 wk after STZ injection. Periodic acid-Schiff staining, Masson staining, and silver staining were performed for renal pathological analyses. In addition, the renal ultrastructure was observed by electron microscope. The activities of p38 and ERK signaling in renal cortical tissues were evaluated by Western blotting. NAD+/NADH ratio and NADPH oxidase activity were also measured. Moreover, the expressions of TNF-α, IL-1, and IL-6 were examined. We provide experimental evidence demonstrating that the WldS gene is expressed in kidney cells and protects against the early stage of diabetes-induced renal dysfunction and extracellular matrix accumulation through delaying the reduction of the NAD+/NADH ratio, inhibiting the activation of p38 and ERK signaling, and suppressing oxidative stress as evidenced by the decreased NADPH oxidase activity and lower expression of TNF-α, IL-1, and IL-6.

scholarly journals Raised Neutrophil Phospholipase A2 Activity and Defective Priming of NADPH Oxidase and Phospholipase A2 in Sickle Cell Disease

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3423-3429 ◽  
Author(s):  
Elahe Mollapour ◽  
John B. Porter ◽  
Richard Kaczmarski ◽  
David C. Linch ◽  
Pamela J. Roberts
Keyword(s):  
Steady State ◽  
Nadph Oxidase ◽  
Phospholipase A2 ◽  
Oxidase Activity ◽  
Neutrophil Function ◽  
Cell Disease ◽  
Nadph Oxidase Activity ◽  
Gm Csf ◽  
Tnf Α ◽  
Phospholipase A2 Activity

Abstract Intermittent painful crises due to vasoocclusion are the major clinical manifestation of sickle cell disease (SCD), but subclinical episodes may also occur. There is sparse evidence for the involvement of neutrophils in the pathophysiology of SCD, but production of cytokines by the damaged endothelium might influence neutrophil function and modulate responses to subsequent cytokine exposure. In addition, the activation of neutrophils in the microcirculation could itself exacerbate vasoocclusion. To test whether neutrophil inflammatory responses were altered in SCD, neutrophil phospholipase A2 and NADPH oxidase activity in response to in vitro priming by granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-α (TNF-α) were measured both during and between painful crises. Resting levels of neutrophil phospholipase A2 activity in steady-state SCD (4.0% ± 0.5% of total cell radioactivity) were raised relative to control values (2.0% ± 0.2%, n = 10, P = .008). There was no defect of agonist-stimulated phospholipase A2 or NADPH oxidase activity in steady-state SCD; however, the ability of phospholipase A2 to respond to priming with GM-CSF was attenuated to 63% ± 17% of control values (n = 10,P = .04). Similarly, neutrophil NADPH oxidase activity after priming with GM-CSF and TNF-α was, respectively, 65% ± 11% (n = 7, P = .03) and 57% ± 7% of control (n = 10, P = .007) in steady-state disease, and was further reduced during painful vasoocclusive crises to 34% ± 9% and 25% ± 3% of control for GM-CSF and TNF-α, respectively. These data were not explained by poor splenic function or any racial factor, as normal cytokine responses were seen in splenectomized patients in remission from Hodgkin's disease and in healthy Afro-Caribbean subjects. Abnormal neutrophil cytokine priming responses were not observed in either patients with rheumatoid arthritis or iron-deficiency anemia. Our findings are indicative of an ongoing inflammatory state in SCD between painful crises involving neutrophil activation and an abnormality of cytokine-regulated neutrophil function, which may compromise the host defenses against certain microorganisms.

scholarly journals Raised Neutrophil Phospholipase A2 Activity and Defective Priming of NADPH Oxidase and Phospholipase A2 in Sickle Cell Disease

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3423-3429
Author(s):  
Elahe Mollapour ◽  
John B. Porter ◽  
Richard Kaczmarski ◽  
David C. Linch ◽  
Pamela J. Roberts
Keyword(s):  
Steady State ◽  
Nadph Oxidase ◽  
Phospholipase A2 ◽  
Oxidase Activity ◽  
Neutrophil Function ◽  
Cell Disease ◽  
Nadph Oxidase Activity ◽  
Gm Csf ◽  
Tnf Α ◽  
Phospholipase A2 Activity

Intermittent painful crises due to vasoocclusion are the major clinical manifestation of sickle cell disease (SCD), but subclinical episodes may also occur. There is sparse evidence for the involvement of neutrophils in the pathophysiology of SCD, but production of cytokines by the damaged endothelium might influence neutrophil function and modulate responses to subsequent cytokine exposure. In addition, the activation of neutrophils in the microcirculation could itself exacerbate vasoocclusion. To test whether neutrophil inflammatory responses were altered in SCD, neutrophil phospholipase A2 and NADPH oxidase activity in response to in vitro priming by granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-α (TNF-α) were measured both during and between painful crises. Resting levels of neutrophil phospholipase A2 activity in steady-state SCD (4.0% ± 0.5% of total cell radioactivity) were raised relative to control values (2.0% ± 0.2%, n = 10, P = .008). There was no defect of agonist-stimulated phospholipase A2 or NADPH oxidase activity in steady-state SCD; however, the ability of phospholipase A2 to respond to priming with GM-CSF was attenuated to 63% ± 17% of control values (n = 10,P = .04). Similarly, neutrophil NADPH oxidase activity after priming with GM-CSF and TNF-α was, respectively, 65% ± 11% (n = 7, P = .03) and 57% ± 7% of control (n = 10, P = .007) in steady-state disease, and was further reduced during painful vasoocclusive crises to 34% ± 9% and 25% ± 3% of control for GM-CSF and TNF-α, respectively. These data were not explained by poor splenic function or any racial factor, as normal cytokine responses were seen in splenectomized patients in remission from Hodgkin's disease and in healthy Afro-Caribbean subjects. Abnormal neutrophil cytokine priming responses were not observed in either patients with rheumatoid arthritis or iron-deficiency anemia. Our findings are indicative of an ongoing inflammatory state in SCD between painful crises involving neutrophil activation and an abnormality of cytokine-regulated neutrophil function, which may compromise the host defenses against certain microorganisms.

scholarly journals Neuroprotective Benefits of Exercise and MitoQ on Memory Function, Mitochondrial Dynamics, Oxidative Stress, and Neuroinflammation in D-Galactose-Induced Aging Rats

2021 ◽  
Vol 11 (2) ◽  
pp. 164
Author(s):  
Jae-Hoon Jeong ◽  
Jung-Hoon Koo ◽  
Jang Soo Yook ◽  
Joon-Yong Cho ◽  
Eun-Bum Kang
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Cognitive Impairment ◽  
Nadph Oxidase ◽  
Learning And Memory ◽  
Oxidase Activity ◽  
Mitochondrial Dynamics ◽  
Nadph Oxidase Activity ◽  
Aging Rats ◽  
Positive Effects

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.

scholarly journals Regulation of NADPH Oxidase Activity in Phagocytes

2010 ◽  
Vol 285 (43) ◽  
pp. 33197-33208 ◽  
Author(s):  
Franck Debeurme ◽  
Antoine Picciocchi ◽  
Marie-Claire Dagher ◽  
Didier Grunwald ◽  
Sylvain Beaumel ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nadph Oxidase Activity

MODULATION OF NADPH OXIDASE ACTIVITY

2011 ◽  
Vol 29 ◽  
pp. e315
Author(s):  
A. Schulz ◽  
V. Jankowski ◽  
W. Zidek ◽  
J. Jankowski
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nadph Oxidase Activity
Sign in / Sign up

Export Citation Format

Share Document