Biomaterial Database

Angiotensin II stimulates thick ascending limb superoxide production via protein kinase C(α)-dependent NADPH oxidase activation. 2010

Marcela Herrera, and Guillermo B Silva, and Jeffrey L Garvin

Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA.

Angiotensin II (Ang II) stimulates thick ascending limb (TAL) O₂ production, but the receptor(s) and signaling mechanism(s)involved are unknown. The effect of Ang II on O₂. is generally attributed to the AT₁receptor. In some cells, Ang II stimulates protein kinase C (PKC), whose α isoform (PKCα) can activate NADPH oxidase. We hypothesized that in TALs, Ang II stimulates O₂. via AT₁and PKC α-dependent NADPH oxidase activation.In rat TALs, 1 nM Ang II stimulated O₂. from 0.760.17 to 1.97 0.21 nmol/min/mg (p < 0.001). An AT₁antagonist blocked the stimulatory effect of Ang II on O₂. (0.87 0.25 nmol/min/mg; p < 0.006), whereas an AT₂ antagonist had no effect (2.16 0.133 nmol/min/mg; p < 0.05 versus vehicle). Apocynin, an NADPH oxidase inhibitor, blocked Ang II-stimulated O₂by 90% (p <0.01). Ang II failed to stimulate O₂. in TALs from p47(phox) -/- mice (p < 0.02). Monitored by fluorescence resonance energy transfer, Ang II increased PKC activity from 0.02 0.03 to 0.13 0.02 arbitrary units (p < 0.03). A general PKC inhibitor, GF109203X, blocked the effect of Ang II on O₂(1.47 +/- .21 versus 2.72 +/- .47 nmol/min/mg with Ang II alone; p < 0.03). A PKCα- and ß-selective inhibitor, Gö6976, also blocked the stimulatory effect of Ang II on O₂. (0.59 +/- 0.15 versus 2.05 +/- 0.28 nmol/min/mg with Ang II alone; p < 0.001). To distinguish between PKC α and PKC ß, we used tubules expressing dominant-negative PKC α or -ß. In control TALs, Ang II stimulated O2. by 2.17 0.44 nmol/min/mg (p < 0.011). In tubules expressing dominant-negative PKC α, Ang II failed to stimulate O2. (change: -0.30 +/- 0.27 nmol/min/mg). In tubules expressing dominant-negative PKC ß1, Ang II stimulated O2. by 2.080.69 nmol/min/mg (p < 0.002). We conclude that Ang II stimulates TAL O₂production via activation of AT₁receptors and PKC α-dependent NADPH oxidase.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010100	Oxygen	An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.	Dioxygen,Oxygen-16,Oxygen 16
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005799	Genes, Dominant	Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.	Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant
D000804	Angiotensin II	An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.	Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000809	Angiotensins	Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.	Angiotensin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013481	Superoxides	Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.	Superoxide Radical,Superoxide,Superoxide Anion
D015971	Gene Expression Regulation, Enzymologic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.	Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic