Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang II could induce mitochondrial oxidative damage that in turn might decrease endothelial nitric oxide (NO˙) bioavailability and promote vascular oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial respiration, membrane potential, glutathione, and endothelial NO˙ was studied in isolated mitochondria and intact bovine aortic endothelial cells using electron spin resonance, dihydroethidium high-performance liquid chromatography –based assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased mitochondrial H2O2 production. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of peroxynitrite), chelerythrine (protein kinase C inhibitor), NG-nitro-l-arginine methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial ATP-sensitive potassium channels inhibitor), or glibenclamide. Depletion of p22phox subunit of NADPH oxidase with small interfering RNA also inhibited Ang II–mediated mitochondrial ROS production. Ang II depleted mitochondrial glutathione, increased state 4 and decreased state 3 respirations, and diminished mitochondrial respiratory control ratio. These responses were attenuated by apocynin, 5-hydroxydecanoate, and glibenclamide. In addition, 5-hydroxydecanoate prevented the Ang II–induced decrease in endothelial NO˙ and mitochondrial membrane potential. Therefore, Ang II induces mitochondrial dysfunction via a protein kinase C–dependent pathway by activating the endothelial cell NADPH oxidase and formation of peroxynitrite. Furthermore, mitochondrial dysfunction in response to Ang II modulates endothelial NO˙ and &OV0151; generation, which in turn has ramifications for development of endothelial dysfunction.

Abstract 1229: Molecular Mechanisms of Angiotensin II-Mediated Mitochondrial Dysfunction: Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction

Significance: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. Recent Advances: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. Critical Issues: The review summarizes the critical sources of oxidative stress in the kidney during injury/disease, including generation of ROS and...

Oxidant Mechanisms in Renal Injury and Disease

In the phagocytosis field, ROS production by the phagocyte NOX has been associated with pathogen killing for the last 50 years. Since the discovery of nonphagocyte NOX, numerous other roles for ROS production have been identified. Oxidative stress and ROS-mediated signaling have received much attention in recent years. Much lower concentrations of ROS may be required for signaling compared with microbial killing. Based on the discoveries in nonphagocytic cells, it became logical to look for ROS functions distinct from pathogen killing, even in phagocytes. ROS are now linked to various forms of cell death, to chemotaxis, and to numerous modifications of cellular processes, including the NOX itself. ROS functions are clearly concentration-dependent over a wide range of concentrations. How much is required for which function? Which species are required for how much time? Is ROS signaling only a side effect of bactericidal ROS production? One major obstacle to answer these questions is the difficulty of reliable quantitative ROS detection. Signal transduction often takes place on a subcellular scale over periods of seconds or minutes, so the detection methods need to provide appropriate time and space resolution. We present examples of local ROS production, decreased degradation, signaling events, and potentially ROS-sensitive functions. We attempt to illustrate the current limitations for quantitative spatiotemporal ROS detection and point out directions for ongoing development. Probes for localized ROS detection and for combined detection of ROS, together with protein localization or other cellular parameters, are constantly improved.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1189/jlb.1012544

ROS production in phagocytes: why, when, and where?

ROS are a group of small reactive molecules that play critical roles in the regulation of various cell functions and biological processes. In the vascular system, physiological levels of ROS are essential for normal vascular functions including endothelial homeostasis and smooth muscle cell contraction. In contrast, uncontrolled overproduction of ROS resulting from an imbalance of ROS generation and elimination leads to the development of vascular diseases. Excessive ROS cause vascular cell damage, the recruitment of inflammatory cells, lipid peroxidation, activation of metalloproteinases and deposition of extracellular matrix, collectively leading to vascular remodelling. Evidence from a large number of studies has revealed that ROS and oxidative stress are involved in the initiation and progression of numerous vascular diseases including hypertension, atherosclerosis, restenosis and abdominal aortic aneurysm. Furthermore, considerable research has been implemented to explore antioxidants that can reduce ROS production and oxidative stress in order to ameliorate vascular diseases. In this review, we will discuss the nature and sources of ROS, their roles in vascular homeostasis and specific vascular diseases and various antioxidants as well as some of the pharmacological agents that are capable of reducing ROS and oxidative stress. The aim of this review is to provide information for developing promising clinical strategies targeting ROS to decrease cardiovascular risks. Linked articles This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Reactive oxygen species: key regulators in vascular health and diseases.

Chronic kidney disease (CKD) remains a worldwide public health problem associated with serious complications and increased mortality rates. Accumulating evidence indicates that elevated intracellular levels of reactive oxygen species (ROS) play a major role in the pathogenesis of CKD. Increased intracellular levels of ROS can lead to oxidation of lipids, DNA, and proteins, contributing to cellular damage. On the other hand, ROS are also important secondary messengers in cellular signaling. Consequently, normal kidney cell function relies on the “right” amount of ROS. Mitochondria and NADPH oxidases represent major sources of ROS in the kidney, but renal antioxidant systems, such as superoxide dismutase, catalase, or glutathione peroxidase counterbalance ROS-mediated injury. This review discusses the main sources of ROS and antioxidant systems in the kidney, and redox signaling pathways leading to inflammation and fibrosis, which result in abnormal kidney function and CKD progression. We further discuss the important role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating antioxidant responses, and other mechanisms of redox signaling.

https://www.mdpi.com/2073-4409/9/6/1342/pdf

Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease.

The mitochondria-rich epithelial cells of the renal medullary thick ascending limb (mTAL) reabsorb nearly 25% of filtered sodium (Na+) and are a major source of cellular reactive oxygen species. Al...

Increase of sodium delivery stimulates the mitochondrial respiratory chain H2O2 production in rat renal medullary thick ascending limb

Objectives:Blockade of the T-type calcium channel (TCC), which is expressed in the renal efferent arterioles of the juxtamedullary nephron and vasa recta, has been shown to protect against renal injury. Studies were designed to determine the effects of a specific TCC blocker, R(−) efonidipine [R(−)E

Role of specific T-type calcium channel blocker R(-) efonidipine in the regulation of renal medullary circulation.

medullary thick ascending limb production in rat renal 2 O 2 respiratory chain H Increase of sodium delivery stimulates the mitochondrial

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Yi Lu

Author Tools

Chat about Author

Papers

Increase of sodium delivery stimulates the mitochondrial respiratory chain H2O2 production in rat renal medullary thick ascending limb

Role of specific T-type calcium channel blocker R(-) efonidipine in the regulation of renal medullary circulation.

medullary thick ascending limb production in rat renal 2 O 2 respiratory chain H Increase of sodium delivery stimulates the mitochondrial