TITLE

VASCULAR BIOLOGY - HEMODYNAMICS - HYPERTENSION Hyperhomocysteinemia activates NF-κB and inducible nitric oxide synthase in the kidney

AUTHOR(S)
Zhang, Fan; Siow, Yaw L.; O, Karmin
PUB. DATE
April 2004
SOURCE
Kidney International;Apr2004, Vol. 65 Issue 4, p1327
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Hyperhomocysteinemia activates NF-κB and inducible nitric oxide synthase in the kidney. Background. Hyperhomocysteinemia is an independent risk factor for cardiovascular disorders. Injury of multiple organs, including the kidney, was observed in hyperhomocysteinemic individuals. Activation of a transcription factor, namely, nuclear factor kappa B (NF-κB), plays an important role in inflammatory response and can exacerbate organ injury. The objective of the present study was to investigate the effect of hyperhomocysteinemia on renal NF-κB activation and the consequence of such activation. Methods. Hyperhomocysteinemia was induced in Sprague-Dawley rats after 4 weeks of a high-methionine diet. Activation of NF-κB was determined by electrophoretic mobility shift assay. Role of inhibitor protein IκBα was examined by Western immunoblotting analysis. Results. There was a significant increase in the level of phosphorylated IκBα protein in kidneys of hyperhomocysteinemic rats. This resulted in a decrease in the IκBα protein level leading to NF-κB activation. As a consequence, the expression of inducible nitric oxide synthase (iNOS) mRNA and protein was significantly elevated in kidneys of hyperhomocysteinemic rats. Increased nitric oxide production (150% of the control) resulted in peroxynitrite formation in these kidneys. Pretreatment of rats with a NF-κB inhibitor not only abolished NF-κB activation, but also reversed hyperhomocysteinemia-induced iNOS expression in the kidney. Conclusion. Hyperhomocysteinemia alone can activate NF-κB and hence induce iNOS-mediated nitric oxide production in the kidney leading to increased peroxynitrite formation. This may represent one of the mechanisms for renal dysfunction in hyperhomocysteinemia.
ACCESSION #
12472456

 

Related Articles

  • The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Jahangir, Eiman; Vita, Joseph A.; Handy, Diane; Palmisano, Joseph; Loscalzo, Joseph; Eberhardt, Robert T. // Vascular Medicine;2009, Vol. 14 Issue 3, p239 

    Studies with L-arginine supplementation have shown inconsistent effects on endothelial function. The generation of guanidinoacetate (GAA) from L-arginine with subsequent formation of creatine and homocysteine and consumption of methionine may reduce the pool of L-arginine available for nitric...

  • The 894G>T variant in the endothelial nitric oxide synthase gene and spina bifida risk. van der Linden, Ivon J. M.; Heil, Sandra G.; den Heijer, Martin; Blom, Henk J. // Journal of Human Genetics;Jun2007, Vol. 52 Issue 6, p516 

    The 894G>T single nucleotide polymorphism (SNP) in the endothelial NOS ( NOS3) gene, has recently been associated with embryonic spina bifida risk. In this study, a possible association between the NOS3 894G>T SNP and spina bifida risk in both mothers and children in a Dutch population was...

  • Nitric Oxide and Dietary Factors: Part III Minerals, Vitamins and Other Dietary and Lifestyle Factors. Toda, Noboru // Vascular Disease Prevention;Jan2007, Vol. 4 Issue 1, p59 

    Full Text Available

  • Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD. Villadsen, Morten M.; Bünger, Mathias H.; Carstens, Mette; Stenkjær, Liselotte; Langdahl, Bente L. // Osteoporosis International;Apr2005, Vol. 16 Issue 4, p411 

    Osteoporosis is a common disease with a strong genetic component. Linkage studies have suggested linkage between BMD and loci on chromosome 1. The MTHFR gene is located on chromosome 1. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used...

  • The use of inhaled nitric oxide and prone position in an ARDS patient with severe traumatic brain injury during spine stabilization. Gritti, Paolo; Lanterna, Luigi; Re, Mariachiara; Martchenko, Svetlana; Olivotto, Paola; Brembilla, Carlo; Agostinis, Cristina; Paganoni, Guido; Lorini, Ferdinando // Journal of Anesthesia;2013, Vol. 27 Issue 2, p293 

    The use of inhaled nitric oxide in patients with traumatic brain injury, intracranial hypertension, and acute respiratory distress syndrome (ARDS) has been reported in an intensive care unit setting only in a few case reports. The use of the prone position for patients with traumatic brain...

  • Exogenous Hydrogen Sulfide (H2S) Protects Alveolar Growth in Experimental O2-Induced Neonatal Lung Injury. Vadivel, Arul; Alphonse, Rajesh S.; Ionescu, Lavinia; Machado, Desiree S.; O’Reilly, Megan; Eaton, Farah; Haromy, Al; Michelakis, Evangelos D.; Thébaud, Bernard // PLoS ONE;Mar2014, Vol. 9 Issue 3, p1 

    Background: Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT). Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S),...

  • Clinical Clips. DiLoreto, Stacy // Patient Care;May2002, Vol. 36 Issue 7, p86 

    Presents the results of several studies on various diseases and injuries. Relation of plasma homocysteine levels to the risk of having dementia and Alzheimer's disease; Residual lifetime risk of hypertension; Treatments for tennis elbow.

  • Homocysteine and hypertension in persons with spinal cord injury. Lee, M. Y.; Myers, J.; Abella, J.; Froelicher, V. F.; Perkash, I.; Kiratli, B. J. // Spinal Cord;Aug2006, Vol. 44 Issue 8, p474 

    Study design:Cross-sectional analysis of a convenience sample of locally recruited participants, including both patients and volunteers.Objectives:To determine whether there is an association between plasma homocysteine and hypertension in persons with spinal cord injury (SCI).Setting:Spinal...

  • A proteomics study of hyperhomocysteinemia injury of the hippocampal neurons using iTRAQ. MIN FANG; JING WANG; HAN YAN; YAN-XIN ZHAO; XUE-YUAN LIU // Molecular Medicine Reports;2014, Vol. 10 Issue 5, p2511 

    High levels of homocysteine, caused by abnormal methionine metabolism, can induce degeneration of mouse hippocampal neurons. iTRAQâ„¢ technology has been widely used in the field of proteomics research and through employing this technology, the present study identified that...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics