Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease

Irazabal, María V.; Torres, Vicente E.

doi:10.3390/cells9061342

Cited by 184 publications

(133 citation statements)

References 121 publications

(130 reference statements)

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“…Ischemic acute kidney injury (AKI) is a frequent complication that is caused by acute limitation or deprivation of arterial blood flow to the kidneys, particularly by restoration of renal blood supply, and AKI is causatively associated with the development of chronic kidney diseases (CKD) [ [199] , [200] , [201] ]. It has been proposed that excessive production of ROS and TNF-α as well as elevation in intracellular Ca 2+ concentration in kidney cells represent important pathological factors, and that cell death, both apoptotic and necrotic, acts as an important cellular mechanism in the pathogenesis of AKI.…”

Section: Trpm2 In Kidney Cell Death Associated With Acute Kidney Injumentioning

confidence: 99%

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Malko

Jiang

2020

Redox Biology

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Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is a non-selective Ca 2+ -permeable cation channel with a wide distribution throughout the body and is highly sensitive to activation by oxidative stress. Recent studies have collected abundant evidence to show its important role in mediating cell death induced by miscellaneous oxidative stress-inducing pathological factors, both endogenous and exogenous, including ischemia/reperfusion and the neurotoxicants amyloid-β peptides and MPTP/MPP + that cause neuronal demise in the brain, myocardial ischemia/reperfusion, proinflammatory mediators that disrupt endothelial function, diabetogenic agent streptozotocin and diabetes risk factor free fatty acids that induce loss of pancreatic β-cells, bile acids that damage pancreatic acinar cells, renal ischemia/reperfusion and albuminuria that are detrimental to kidney cells, acetaminophen that triggers hepatocyte death, and nanoparticles that injure pericytes. Studies have also shed light on the signalling mechanisms by which these pathological factors activate the TRPM2 channel to alter intracellular ion homeostasis leading to aberrant initiation of various cell death pathways. TRPM2-mediated cell death thus emerges as an important mechanism in the pathogenesis of conditions including ischemic stroke, neurodegenerative diseases, cardiovascular diseases, diabetes, pancreatitis, chronic kidney disease, liver damage and neurovascular injury. These findings raise the exciting perspective of targeting the TRPM2 channel as a novel therapeutic strategy to treat such oxidative stress-associated diseases.

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Section: Trpm2 In Kidney Cell Death Associated With Acute Kidney Injumentioning

confidence: 99%

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Malko

Jiang

2020

Redox Biology

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“…Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to glomerulus or renal tubules [1]. Renal fibrosis is the common pathway of all kinds of CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin (FN) and collagen I (Col-I) in interstitial areas [2,3].…”

mentioning

confidence: 99%

Renal asymmetric dimethylarginine inhibits fibrosis

Yuan

Yanzhe

et al. 2020

FEBS Open Bio

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Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and collagen I, in interstitial areas. Indirect in vivo experimental data suggest that renal asymmetric dimethylarginine (ADMA) exerts antifibrotic activity in CKD. In this study, we aimed to demonstrate that renal ADMA has a direct effect on fibrosis in vivo . Normal saline, ADMA, nonsense control siRNA, Ddah1 siRNA or Ddah2 siRNA was administered into the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested at day 1 or 7. Western blotting was performed to assess the expression of ADMA, DDAH1 and DDAH2 and the expression of fibrotic markers, such as fibronectin, collagen I, α‐smooth muscle actin, phosphorylation of Smad3 and connective tissue growth factor. Masson’s trichrome staining was used to further evaluate renal fibrosis. We observed that intrarenal administration of ADMA increased the renal accumulation of ADMA and attenuated renal fibrosis at days 1 and 7. Knockdown of Ddah1 or Ddah2 increased the amount of ADMA in UUO kidneys and inhibited the expression of fibrotic proteins at days 1 and 7, which was further confirmed by Masson’s staining. Thus, our in vivo data suggest that renal ADMA exerts direct antifibrotic effects in a mouse model of UUO.

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“…Protonation of hydrogen peroxide (ROOH) forms hydrogen peroxide (H 2 O 2 ) which, furthermore, cleaves into hydroxy radicals (OH • ). The redox cycling produces free radical semiquinone from quinoid substrates [ 103 ]. In the mitochondrial transport chain, flavoprotein reductase forms ROS by direct reduction of O 2 and via the mediation of quinones.…”

Section: Oxidative Stressmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka

Vécsei

2020

Biomedicines

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Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.

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Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease

Cited by 184 publications

References 121 publications

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Renal asymmetric dimethylarginine inhibits fibrosis

Monitoring the Redox Status in Multiple Sclerosis

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