Abstract:
AIMS:Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Emerging evidence suggests that plasma ADMA accumulation and DDAH1 activity/expression reduction are linked to chronic kidney disease (CKD) pathology, but the mechanisms remain largely unknown. Here, we examined the role of ADMA/DDAH1 in the epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs), an important mechanism for the pathogenesis of renal fibrosis. RESULTS:In HK-2 cells, DDAH1 expression was reduced by aldosterone treatment, and overexpression of DDAH1 significantly attenuated aldosterone-induced EMT. More interestingly, DDAH1 deficiency resulted in EMT-related changes in primary TECs via increasing oxidative stress, impairing adenosine monophosphate-activated kinase (AMPK) signaling, and downregulating of peroxiredoxin 5 (Prdx5). However, those effects could not be mimicked by increasing the ADMA concentration. After regular feeding for 24 months or inducing type 2 diabetes, Ddah1-/- mice had higher serum creatinine levels than wild-type (WT) mice. In the kidneys of the aged or diabetic mice, loss of DDAH1 resulted in more interstitial fibrosis, more collagen deposition, and greater induction of EMT-related changes and oxidative stress than in the WT kidneys. Innovation and Conclusion: Our results provide the first direct evidence that the DDAH1 has a marked effect on kidney fibrosis and oxidative stress induced by aging or diabetes. Our findings suggest that strategies to increase DDAH1 activity in TECs may provide a novel approach to attenuate CKD development. Antioxid. Redox Signal. 27, 1347-1360.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Shi L,Zhao C,Wang H,Lei T,Liu S,Cao J,Lu Zdoi
10.1089/ars.2017.7022subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1347-1360issue
16eissn
1523-0864issn
1557-7716journal_volume
27pub_type
杂志文章abstract:AIMS:Recent studies have shown that cigarette smoke (CS)-induced oxidative stress impairs autophagy, resulting in aggresome-formation that correlates with severity of chronic obstructive pulmonary disease (COPD)-emphysema, although the specific step in autophagy pathway that is impaired is unknown. Hence, in this study...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6842
更新日期:2017-07-20 00:00:00
abstract::Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.347
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abstract::Pulmonary surfactant, a complex of lipids and proteins, maintains alveolar integrity and participates in the control of host defense and inflammation in the lung. Surfactant proteins A, B, C, and D are important components of surfactant that play diverse roles in the surface tension reducing as well as host defense an...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308604771978499
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abstract::Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2034
更新日期:2008-12-01 00:00:00
abstract:SIGNIFICANCE:Chagas disease (CD) affects several million people in Latin America and is spreading beyond its classical boundaries due to the migration of infected host and insect vectors, HIV co-infection, and blood transfusion. The current therapy is not adequate for treatment of the chronic phase of CD, and new drugs...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4618
更新日期:2013-09-01 00:00:00
abstract::Despite the significance of redox post-translational modifications (PTMs) in regulating diverse signal transduction pathways, the enzymatic systems that catalyze reversible and specific oxidative or reductive modifications have yet to be firmly established. Thioredoxin 1 (Trx1) is a conserved antioxidant protein that ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3831
更新日期:2011-11-01 00:00:00
abstract:: Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including we...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8059
更新日期:2021-01-10 00:00:00
abstract:AIMS:While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5142
更新日期:2013-11-10 00:00:00
abstract::Although there is an abundance of evidence suggesting that insulin resistance plays a significant role in the vasculature, the precise mechanistic role involved still remains unclear. In this review, we discuss the current background of insulin resistance in the context of insulin signaling and action in the vasculatu...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1053
更新日期:2005-07-01 00:00:00
abstract:: Significance: Nuclear factor erythroid 2 (NFE2)-related factor 2 (NFE2L2, or NRF2) is a transcription factor predominantly affecting the expression of antioxidant genes. NRF2 plays a significant role in the control of redox balance, which is crucial in cancer cells. NRF2 a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8024
更新日期:2020-11-01 00:00:00
abstract::Chronic inflammatory processes induce oxidative stress and lipid peroxidation (LPO), hereby generating DNA-reactive aldehydes such as trans-4-hydroxy-2-nonenal (HNE). Etheno-modified DNA bases are inter alia generated by reaction of DNA with HNE. Using an immunoaffinity-(32)P-postlabeling method, the authors have inve...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.8.1003
更新日期:2006-05-01 00:00:00
abstract:SIGNIFICANCE:Pyridine dinucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), were discovered more than 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variet...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7120
更新日期:2018-01-20 00:00:00
abstract:UNLABELLED:In living systems, the mechanisms of inheritance involving gene expression are operated by (i) the traditional model of genetics where the deoxyribonucleic acid (DNA) transcription and messenger ribonucleic acid stability are influenced by the DNA sequences and any aberrations in the primary DNA sequences an...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4600
更新日期:2012-07-15 00:00:00
abstract::Homocysteine is a thiol-containing amino acid that has gained notoriety because its elevation in the plasma is correlated with complex and multifactorial diseases, including cardiovascular diseases, neurodegenerative diseases, and neural tube defects. Homocysteine is redox-active, and its toxic effects have been frequ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.547
更新日期:2005-05-01 00:00:00
abstract:SIGNIFICANCE:Worldwide demand has driven the development of hemoglobin (Hb)-based oxygen carriers (HBOCs) as potential acellular oxygen therapeutics. HBOCs have the potential to provide an oxygen bridge to patients and minimize current problems associated with supply and storage of donated blood. However, to date, safe...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6805
更新日期:2017-05-10 00:00:00
abstract:SIGNIFICANCE:The accepted effects of aging in mammalian skeletal muscle are progressive atrophy and weakening, or sarcopenia. Canonical hallmarks of aging in skeletal muscle include a reduction in muscle fiber cross-sectional area, a loss in muscle fibers through apoptosis and denervation, and infiltration of connectiv...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3974
更新日期:2011-11-01 00:00:00
abstract::Cells oxidize molecules to generate energy and to make the materials to build and support the structures and functions needed for life. However, unwanted oxidations can damage these same structures and impair function. Lipids (the lipids in membranes and lipoproteins) are targets of unwanted oxidations. The primary me...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308604773934396
更新日期:2004-06-01 00:00:00
abstract:: Significance: Genomic instability, a hallmark of cancer, renders cancer cells susceptible to genomic stress from both endogenous and exogenous origins, resulting in the increased tendency to accrue DNA damage, chromosomal instability, or aberrant DNA localization. Apart fr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8221
更新日期:2020-12-04 00:00:00
abstract::Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and infl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2097
更新日期:2009-02-01 00:00:00
abstract:SIGNIFICANCE:Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids,...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7123
更新日期:2017-11-20 00:00:00
abstract::Heme oxygenase (HO)-1, involved in the heme degradation process, is an important antioxidant enzyme. The induction of HO-1 gene expression, in response to diverse oxidative stimuli, represents a critical event in adaptive cellular response. Experimental models of various diseases, including acute inflammation, atheros...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1688
更新日期:2005-11-01 00:00:00
abstract::Thioredoxin (TRX) family proteins are involved in various biologic processes by regulating the response to oxidative stress. Nucleoredoxin (NRX), a relatively uncharacterized member of the TRX family protein, has recently been reported to regulate the Wnt/beta-catenin pathway, which itself regulates cell fate and earl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1550
更新日期:2007-08-01 00:00:00
abstract:AIMS:Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. RESULTS:We demonstrate that Her2high cells and t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6677
更新日期:2017-01-10 00:00:00
abstract::DJ-1 is a member of the large and functionally diverse DJ-1/PfpI superfamily and has homologs in nearly all organisms. Because of its connection to parkinsonism and cancer, human DJ-1 has been intensely studied for over a decade. The current view is that DJ-1 is a multifunctional oxidative stress response protein that...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3481
更新日期:2011-07-01 00:00:00
abstract:AIM:TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend(®) can sensitize tumor cells to TRAIL. RESULTS:We found that...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3982
更新日期:2012-03-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia and a progressive neurodegeneration that appears to result from multiple pathogenic mechanisms (including protein misfolding/aggregation, involved in both amyloid β-dependent senile plaques and tau-dependent neurofibrillary tangles), metabolic and mitochond...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4082
更新日期:2012-05-01 00:00:00
abstract:SIGNIFICANCE:MicroRNAs (miRNAs) are important regulators of gene expression and define part of the epigenetic signature. Their influence on every realm of biomedicine is established and progressively increasing. The impact of environment on human health is enormous. Among environmental risk factors impinging on quality...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7175
更新日期:2018-03-20 00:00:00
abstract::Cellular redox balance is vital in health and disease. In this Forum, we highlight the importance of reactive oxygen species (ROS) in the regulation of redox balance in different organ systems of the body and ROS contribution to the development of hypertension. The Forum examines interactions between oxidative and nit...
journal_title:Antioxidants & redox signaling
pub_type: 社论
doi:10.1089/ars.2013.5591
更新日期:2014-01-01 00:00:00
abstract::Vascular complications in diabetes are a significant source of human morbidity and mortality, affecting multiple organ systems and persisting despite tight glucose control. Many of these complications can be linked to impairments in vasculogenesis, the process by which circulating and bone marrow-derived endothelial p...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1476
更新日期:2005-11-01 00:00:00
abstract:SIGNIFICANCE:Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metaboli...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6705
更新日期:2017-09-20 00:00:00