5-Lipoxygenase is involved in the angiotensin II-induced NAD(P)H-oxidase activation. 2003

Maren Luchtefeld, and Helmut Drexler, and Bernhard Schieffer
Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Germany.

Angiotensin II (ANG II)-induced interleukin (IL)-6 synthesis requires NAD(P)H-oxidase-derived superoxide anions. Since NAD(P)H-oxidase activation by cytokines involves 5-lipoxygenase (LOX)-derived leukotriene B(4) (LTB(4)) formation, we postulated that LTB(4) is involved in the ANG II-dependent NAD(P)H-oxidase activation. Therefore, 5-LOX expression and LTB(4) formation following ANG II (100nM) stimulation were determined in rat aortic smooth muscle cells (SMC). Reactive oxygen species (ROS)-formation and IL-6 mRNA expression were analyzed following ANG II and LTB(4) (0.6 microM) stimulation. 5-LOX mRNA and protein were detected in SMC. ANG II-induced LTB(4) formation at 2.5min and was followed by an increase in ROS-formation and IL-6 mRNA expression. Blockade of 5-LOX by MK886 (200nM) abrogated LTB(4)-formation, ROS-formation, and IL-6 mRNA expression. Moreover, LTB(4)-induced ROS-formation and IL-6 mRNA expression was abolished by NAD(P)H-oxidase inhibition using diphenyleneiodonium chloride (DPI 10 microM). In conclusion, the present study demonstrates that ANG II enhances LTB(4)-formation in an 5-LOX dependent manner. LTB(4) activates the vascular type NAD(P)H-oxidase, leading to an increase in IL-6 transcripts.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007975 Leukotriene B4 The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990) 5,12-HETE,5,12-diHETE,LTB4,Leukotriene B,Leukotriene B-4,Leukotrienes B,5,12 HETE,5,12 diHETE,B-4, Leukotriene,Leukotriene B 4
D008297 Male Males
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
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
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
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
D001094 Arachidonate 5-Lipoxygenase An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes. 5-Lipoxygenase,Arachidonic Acid 5-Lipoxygenase,LTA4 Synthase,Leukotriene A Synthase,Leukotriene A4 Synthase,Leukotriene A4 Synthetase,5 Lipoxygenase,5-Lipoxygenase, Arachidonate,5-Lipoxygenase, Arachidonic Acid,Arachidonate 5 Lipoxygenase,Arachidonic Acid 5 Lipoxygenase,Synthase, LTA4,Synthase, Leukotriene A,Synthase, Leukotriene A4,Synthetase, Leukotriene A4

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