The functional significance of NOX1/NADPH oxidase in the heart has not been explored due to its low expression relative to other NOX homologs identified so far. We aimed to clarify the role of NOX1/NADPH oxidase in the septic heart by utilizing mice deficient in the Nox1 gene (Nox1(-/Y)). Sepsis was induced by intraperitoneal administration of lipopolysaccharides (LPS: 25mg/kg) or cecal ligation and puncture (CLP) surgery. A marked elevation of NOX1 mRNA was demonstrated in cardiac tissue, which was accompanied by increased production of reactive oxygen species (ROS). In Nox1(-/Y) treated with LPS, cardiac dysfunction and survival were significantly improved compared with wild-type mice (Nox1(+/Y)) treated with LPS. Concomitantly, LPS-induced cardiomyocyte apoptosis and activation of caspase-3 were alleviated in Nox1(-/Y). The level of phosphorylated Akt in cardiac tissue was significantly lowered in Nox1(+/Y) but not in Nox1(-/Y) treated with LPS or that underwent CLP surgery. Increased oxidation of cysteine residues of Akt and enhanced interaction of Akt with protein phosphatase 2A (PP2A), a major phosphatase implicated in the dephosphorylation of Akt, were demonstrated in LPS-treated Nox1(+/Y). These responses to LPS were significantly attenuated in Nox1(-/Y). Taken together, ROS derived from NOX1/NADPH oxidase play a pivotal role in endotoxin-induced cardiomyocyte apoptosis by increasing oxidation of Akt and subsequent dephosphorylation by PP2A. Marked up-regulation of NOX1 may affect the risk of mortality under systemic inflammatory conditions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.freeradbiomed.2012.08.590 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NADPH oxidase 1 promotes hepatic steatosis in obese mice and is abrogated by augmented skeletal muscle mass.
Am J Physiol Gastrointest Liver Physiol
March 2024
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia, United States.
Exercise as a lifestyle modification is a frontline therapy for nonalcoholic fatty liver disease (NAFLD), but how components of exercise attenuate steatosis is unclear. To uncouple the effect of increased muscle mass from weight loss in obesity, myostatin knockout mice were bred on a lean and obese background. Myostatin deletion increases gastrocnemius (Gastrocn.
View Article and Find Full Text PDFRole of the CCL5 and Its Receptor, CCR5, in the Genesis of Aldosterone-Induced Hypertension, Vascular Dysfunction, and End-Organ Damage.
Hypertension
April 2024
Department of Pediatrics at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh, (R.M.C., D.M.C., A.B.-N., J.V.A., W.M.C.A., S.S., J.H., T.B.-N.), University of Pittsburgh, PA.
Background: Aldosterone has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The functions of CCL5 (C-C motif chemokine ligand 5) and its receptor CCR5 (C-C motif chemokine receptor 5) are well known in infectious diseases, their contributions to aldosterone-induced vascular injury and hypertension remain unknown.
Methods: We analyzed the vascular profile, blood pressure, and renal damage in wild-type (CCR5) and CCR5 knockout (CCR5) mice treated with aldosterone (600 µg/kg per day for 14 days) while receiving 1% saline to drink.
Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels.
Hypertension
April 2024
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
Vascular inflammation underlies the development of hypertension, and the mechanisms by which it increases blood pressure remain the topic of intense investigation. Proinflammatory factors including glucose, salt, vasoconstrictors, cytokines, wall stress, and growth factors enhance contractility and impair relaxation of vascular smooth muscle cells. These pathways share a dependence upon redox signaling, and excessive activation promotes oxidative stress that promotes vascular aging.
View Article and Find Full Text PDFType 1 Diabetes Impairs Endothelium-Dependent Relaxation Via Increasing Endothelial Cell Glycolysis Through Advanced Glycation End Products, PFKFB3, and Nox1-Mediated Mechanisms.
Hypertension
October 2023
Vascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.
Background: Type 1 diabetes (T1D) is a major cause of endothelial dysfunction. Although cellular bioenergetics has been identified as a new regulator of vascular function, whether glycolysis, the primary bioenergetic pathway in endothelial cells (EC), regulates vascular tone and contributes to impaired endothelium-dependent relaxation (EDR) in T1D remains unknown.
Methods: Experiments were conducted in Akita mice with intact or selective deficiency in EC PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), the main regulator of glycolysis.
[NOX1/NADPH Oxidase Facilitates Repetitive Behaviors by Enhancing D Receptor-mediated Synaptic Potentiation in the Striatum].
Yakugaku Zasshi
November 2022
Department of Pharmacology, Graduate School of Medicine, Kyoto University.
Repetitive behavior, a form of compulsivity, is a component of several neuropsychiatric disorders, including obsessive-compulsive disorder and addiction. Dysfunction of dopaminergic modulation in the striatum is thought to be a key neural mechanism underlying compulsive behavior repetition; however, the mechanistic links between dopaminergic abnormalities and compulsivity remain unclear. This review discusses our recent work demonstrating the contribution of the NOX1 isoform of the superoxide-producing enzyme, nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), to compulsive-like repetitive behavior in mice that received repeated stimulation of D receptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!