scholarly journals Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Cheng Wan ◽  
Hua Su ◽  
Chun Zhang
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Nadph Oxidase ◽  
Renal Injury ◽  
Mesangial Cells ◽  
Therapeutic Strategies ◽  
Metabolic Factors ◽  
Glomerular Diseases ◽  
Increased Risk

Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies.

scholarly journals Impact of Oxidative Stress in Fetal Programming

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Loren P. Thompson ◽  
Yazan Al-Hasan
Keyword(s):  
Oxidative Stress ◽  
Organ Dysfunction ◽  
Fetal Programming ◽  
Target Genes ◽  
Therapeutic Strategies ◽  
Epigenetic Mechanisms ◽  
Adult Disease ◽  
Specific Target ◽  
Increased Risk

Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

scholarly journals Sesamol Ameliorates Renal Injury-Mediated Atherosclerosis Via Inhibition of Oxidative Stress/IKKα/p53

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1519
Author(s):  
Jie-Sian Wang ◽  
Ping-Hsuan Tsai ◽  
Kuo-Feng Tseng ◽  
Fang-Yu Chen ◽  
Wen-Chin Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Cell Model ◽  
Premature Death ◽  
Risk Groups ◽  
Protective Role ◽  
Increased Risk ◽  
Stress Burden ◽  
Oil Red O Staining

Patients with chronic kidney disease (CKD) are at an increased risk of premature death due to the development of cardiovascular disease (CVD) owing to atherosclerosis-mediated cardiovascular events. However, the mechanisms linking CKD and CVD are clear, and the current treatments for high-risk groups are limited. In this study, we aimed to examine the effects of sesamol, a natural compound extracted from sesame oil, on the development of atherosclerosis in a rodent CKD model, and reactive oxygen species-induced oxidative damage in an endothelial cell model. ApoE–/– mice were subjected to 5/6 nephrectomy (5/6 Nx) and administered sesamol for 8 weeks. Compared with the sham group, the 5/6 Nx ApoE–/– mice showed a significant increase in malondialdehyde levels and Oil Red O staining patterns, which significantly decreased following sesamol administration. Sesamol suppressed H2O2-induced expression of phospho-IKKα, p53, and caspase-3. Our results highlight the protective role of sesamol in renal injury-associated atherosclerosis and the pathological importance of oxidative stress burden in CKD–CVD interaction.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals Comparative Proteomics Analysis of Mouse Habu Nephritis Models with and without Unilateral Nephrectomy

2016 ◽  
Vol 39 (5) ◽  
pp. 1761-1776 ◽  
Author(s):  
Lei Chen ◽  
Yang Lu ◽  
Jun Wen ◽  
Xu Wang ◽  
Lingling Wu ◽  
...  
Keyword(s):  
Renal Injury ◽  
Quantitative Proteomics ◽  
Mesangial Cells ◽  
Unilateral Nephrectomy ◽  
Label Free ◽  
Proteomics Analysis ◽  
Single Kidney ◽  
Regulation Of Actin Cytoskeleton ◽  
Insight Into

Background/Aims: Individuals possessing a single kidney are at greater risk of renal injury upon exposure to harmful stimuli. This study aimed to explore the pathogenesis of renal injury in glomerulonephritis with versus without unilateral nephrectomy (UNX). Methods: Histological analysis and label-free quantitative proteomics were performed on two models—the Habu snake venom-induced glomerulonephritis model with versus without UNX (HabuU and Habu models, respectively). The role of villin 1, a differentially expressed protein (DEP) in mouse mesangial cells, was investigated. Results: Persistent mesangiolysis and focal hypercellularity together with reduced activation of cell proliferation in the HabuU model induced more serious renal injury compared with that in the Habu model. The DEPs between the two models were identified by label-free liquid chromatography-mass spectrometry. The KEGG pathway results indicated that regulation of actin cytoskeleton and focal adhesion were specifically enriched in the HabuU model. The cytoskeleton regulation protein villin 1 was downregulated in the HabuU model, but unchanged in the Habu model. Knockdown of villin 1 promoted apoptosis and inhibited the proliferation of mouse mesangial cells, suggesting villin 1 to be involved in qlomerular lesion self-repair insufficiency. Conclusion: By assessing the proteomic profiles of the two models, this study identified several important differences, particularly villin 1 expression, in regulatory mechanisms between the two models. Our findings provide novel insight into the mechanism of serious renal injury in glomerulonephritis with UNX.

scholarly journals NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sunil Joshi ◽  
Ammon B. Peck ◽  
Saeed R. Khan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tissue Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Renal Tissue ◽  
Oxygen Species ◽  
Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

scholarly journals Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanan Sun ◽  
Cao Ma ◽  
Hui Sun ◽  
Huan Wang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Impaired Insulin ◽  
The Brain

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

scholarly journals Urotensin-II: More Than a Mediator for Kidney

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ayşe Balat ◽  
Mithat Büyükçelik
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Active Role ◽  
Renal Physiology ◽  
Urotensin Ii ◽  
Glomerular Diseases ◽  
Stress Mediators ◽  
And Oxidative Stress

Human urotensin-II (hU-II) is one of the most potent vasoconstrictors in mammals. Although both hU-II and its receptor, GPR14, are detected in several tissues, kidney is a major source of U-II in humans. Recent studies suggest that U-II may have a possible autocrine/paracrine functions in kidney and may be an important target molecule in studying renal pathophysiology. It has several effects on tubular transport and probably has active role in renal hemodynamics. Although it is an important peptide in renal physiology, certain diseases, such as hypertension and glomerulonephritis, may alter the expression of U-II. As might be expected, oxidative stress, mediators, and inflammation are like a devil's triangle in kidney diseases, mostly they induce each other. Since there is a complex relationship between U-II and oxidative stress, and other mediators, such as transforming growth factorβ1 and angiotensin II, U-II is more than a mediator in glomerular diseases. Although it is an ancient peptide, known for 31 years, it looks like that U-II will continue to give new messages as well as raising more questions as research on it increases. In this paper, we mainly discuss the possible role of U-II on renal physiology and its effect on kidney diseases.

scholarly journals Melatonin reduces oxidative damage in mouse granulosa cells via restraining JNK-dependent autophagy

Reproduction ◽  
2018 ◽  
Vol 155 (3) ◽  
pp. 307-319 ◽  
Author(s):  
Yan Cao ◽  
Ming Shen ◽  
Yi Jiang ◽  
Shao-chen Sun ◽  
Honglin Liu
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Mammalian Cells ◽  
Therapeutic Strategies ◽  
Oxygen Species ◽  
Protective Effects ◽  
Follicular Atresia ◽  
Direct Role ◽  
Jnk Pathway

Oxidative stress-induced granulosa cell (GCs) injury is believed to be a common trigger for follicular atresia. Emerging evidence indicates that excessive autophagy occurs in mammalian cells with oxidative damage. N-acetyl-5-methoxytrypamine (melatonin) has been shown to prevent GCs from oxidative injury, although the exact mechanism remains to be elucidated. Here, we first demonstrated that the suppression of autophagy through the JNK/BCL-2/BECN1 signaling is engaged in melatonin-mediated GCs protection against oxidative damage. Melatonin inhibited the loss of GCs viability, formation of GFP-MAP1LC3B puncta, accumulation of MAP1LC3B-II blots, degradation of SQSTM1 and the expression of BECN1, which was correlated with impaired activation of JNK during oxidative stress. On the other hand, blocking of autophagy and/or JNK also reduced the level of H2O2-induced GCs death, but failed to further restore GCs viability in the presence of melatonin. Particularly, the suppression of autophagy provided no additional protective effects when GCs were pretreated with JNK inhibitor and/or melatonin. Importantly, we found that the enhanced interaction between BCL-2 and BECN1 might be a responsive mechanism for autophagy suppression via the melatonin/JNK pathway. Moreover, blocking the downstream antioxidant system of melatonin using specific inhibitors further confirmed a direct role of melatonin/JNK/autophagy axis in preserving GCs survival without scavenging reactive oxygen species (ROS). Taken together, our findings uncover a novel function of melatonin in preventing GCs from oxidative damage by targeting JNK-mediated autophagy, which might contribute to develop therapeutic strategies for patients with ovulation failure-related disorders.

scholarly journals Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases

2020 ◽  
Vol 21 (5) ◽  
pp. 1559 ◽  
Author(s):  
Guangbi Li ◽  
Jason Kidd ◽  
Pin-Lan Li
Keyword(s):  
Structural Integrity ◽  
Hydrolytic Enzymes ◽  
Therapeutic Strategies ◽  
Normal Function ◽  
Current Evidence ◽  
Autophagic Flux ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Membrane Bound

Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.

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