NDLI: NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart

Content Provider	PubMed Central
Author	Kuroda, Junya Ago, Tetsuro Matsushima, Shouji Zhai, Peiyong Schneider, Michael D. Sadoshima, Junichi
Abstract	NAD(P)H oxidases (Noxs) produce O2 − and play an important role in cardiovascular pathophysiology. The Nox4 isoform is expressed primarily in the mitochondria in cardiac myocytes. To elucidate the function of endogenous Nox4 in the heart, we generated cardiac-specific Nox4 −/− (c-Nox4 −/−) mice. Nox4 expression was inhibited in c-Nox4 −/− mice in a heart-specific manner, and there was no compensatory up-regulation in other Nox enzymes. These mice exhibited reduced levels of O2 − in the heart, indicating that Nox4 is a significant source of O2 − in cardiac myocytes. The baseline cardiac phenotype was normal in young c-Nox4 −/− mice. In response to pressure overload (PO), however, increases in Nox4 expression and O2 − production in mitochondria were abolished in c-Nox4 −/− mice, and c-Nox4 −/− mice exhibited significantly attenuated cardiac hypertrophy, interstitial fibrosis and apoptosis, and better cardiac function compared with WT mice. Mitochondrial swelling, cytochrome c release, and decreases in both mitochondrial DNA and aconitase activity in response to PO were attenuated in c-Nox4 −/− mice. On the other hand, overexpression of Nox4 in mouse hearts exacerbated cardiac dysfunction, fibrosis, and apoptosis in response to PO. These results suggest that Nox4 in cardiac myocytes is a major source of mitochondrial oxidative stress, thereby mediating mitochondrial and cardiac dysfunction during PO.
Related Links	http://dx.doi.org/10.1073/pnas.1002178107
Ending Page	15570
Page Count	6
Starting Page	15565
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	35
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-08-31
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Angiotensin II-Induced Mitochondrial Nox4 Is a Major Endogenous Source of Oxidative Stress in Kidney Tubular Cells

Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target

NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Endothelial NOX4 Oxidase Negatively Regulates Inflammation and Improves Morbidity During Influenza A Virus Lung Infection in Mice

Implication of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase and Its Inhibitors in Alzheimer's Disease Murine Models

Oxidative stress in atrial fibrillation: An emerging role of NADPH oxidase

Role of hepatocyte NADPH Oxidase 4 in oxidative stress and DNA damage by genotype 1a hepatitis C virus

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

Corrigendum: Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart

Similar Documents

Angiotensin II-Induced Mitochondrial Nox4 Is a Major Endogenous Source of Oxidative Stress in Kidney Tubular Cells

Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target

NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Endothelial NOX4 Oxidase Negatively Regulates Inflammation and Improves Morbidity During Influenza A Virus Lung Infection in Mice

Implication of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase and Its Inhibitors in Alzheimer's Disease Murine Models

Oxidative stress in atrial fibrillation: An emerging role of NADPH oxidase

Role of hepatocyte NADPH Oxidase 4 in oxidative stress and DNA damage by genotype 1a hepatitis C virus

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

Corrigendum: Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart