Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells

Vejražka, Martin; Mícek, Radan; Stípek, S

doi:10.1016/j.bbagen.2004.12.008

Cited by 152 publications

(126 citation statements)

References 21 publications

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“…We here demonstrate the involvement of NADPH oxidase activity in IL-1-mediated COX-2 expression by showing that DPI blocks IL-1-mediated COX-2 induction. Another NAD(P)H oxidase inhibitor, apocynin, had no effect on EC COX-2 expression, but it is known that apocynin inhibits NAD(P)H oxidase activity only in phagocytes, stimulating ROS production in nonphagocytic cells (31). We observed that DHA treatment of EC led to decreased p47 phox membrane translocation, together with diminished NAD(P)H oxidase activity and intracellular ROS production.…”

Section: Discussionmentioning

confidence: 51%

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Massaro

Habib

Lubrano

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

200

149

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A high intake of the omega-3 fatty acid docosahexaenoate [docosahexaenoic acid (DHA)] has been associated with systemic antiinflammatory effects and cardiovascular protection. Cyclooxygenase (COX)-2 is responsible for the overproduction of prostaglandins (PG) at inflammatory sites, and its expression is increased in atheroma. We studied the effects of DHA on COX-2 expression and activity in human saphenous vein endothelial cells challenged with proinflammatory stimuli. A ≥24-h exposure to DHA reduced COX-2 expression and activity induced by IL-1, without affecting COX-1 expression. DHA effect depended on the NF-κB-binding site in the COX-2 promoter. EMSAs confirmed that DHA attenuated NF-κB activation. Because MAPK, PKC, and NAD(P)H oxidase all participate in IL-1-mediated COX-2 expression, we also tested whether these enzymes were involved in DHA effects. Western blots showed that DHA blocked nuclear p65 NF-κB subunit translocation by decreasing cytokine-stimulated reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase and PKCε activities. Finally, to address the question whether DHA itself or DHA-derived products were responsible for these effects, we inhibited the most important enzymes involved in polyunsaturated fatty acid metabolism, showing that 15-lipoxygenase-1 products mediate part of DHA effects. These studies provide a mechanistic basis for antiinflammatory and possibly plaque-stabilizing effects of DHA

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Section: Discussionmentioning

confidence: 51%

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Massaro

Habib

Lubrano

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

200

149

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“…Earlier reports, however, verified that apocynin decreases NADPH-stimulated O 2 Ϫ generation in the vasculature (9,18,20,22,28,32,54), where apocynin may be activated by peroxidases in vascular cells instead of MPOs (55,56). Since there are abundant cell types in blood and in vascular wall, including granulocyte, MPOs may be present in the vessel wall (56).…”

Section: Discussionmentioning

confidence: 99%

“…Apocynin inhibits the translocation of cytoplasmic units and thereafter blocks the assembly of cytosolic units and NOX (22,40,56). This compound requires an activation by myeloperoxidases (MPOs), which are generally expressed in the granulocyte but not in the vascular cell (25,53).…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase has a directional response to shear stress

Godbole¹,

Lu²,

Guo³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Godbole AS, Lu X, Guo X, Kassab GS. NADPH oxidase has a directional response to shear stress. Am J Physiol Heart Circ Physiol 296: H152-H158, 2009. First published November 14, 2008 doi:10.1152/ajpheart.01251.2007.-Vessel regions with predilection to atherosclerosis have negative wall shear stress due to flow reversal. The flow reversal causes the production of superoxides (O 2 Ϫ ), which scavenge nitric oxide (NO), leading to a decrease in NO bioavailability and endothelial dysfunction. Here, we implicate NADPH oxidase as the primary source of O 2 Ϫ during full flow reversal. Nitrite production and the degree of vasodilation were measured in 46 porcine common femoral arteries in an ex vivo system. Nitrite production and vasodilation were determined before and after the inhibition of NADPH oxidase, xanthine oxidase, or mitochondrial oxidase. NADPH oxidase inhibition with gp91ds-tat or apocynin restored nitrite production and vasodilation during reverse flow. Xanthine oxidase inhibition increased nitrite production at the highest flow rate, whereas mitochondrial oxidase inhibition had no effect. These findings suggest that the NADPH oxidase system can respond to directional changes of flow and is activated to generate O 2 Ϫ during reverse flow in a dose-dependent fashion. These findings have important clinical implications for oxidative balance and NO bioavailability in regions of flow reversal in a normal and compromised cardiovascular system. superoxide; nitric oxide; oxidative balance; reduced nicotinamide adenine dinucleotide phosphate NITRIC OXIDE (NO) is released by endothelial cells to regulate blood vessel diameter acutely as well as to maintain long-term homeostatic conditions of the vessel wall (4,30). NO is produced in the endothelium from L-arginine by the enzyme endothelial NO synthase (eNOS) (4, 41) and is released in response to endothelial shear stress and other stimuli such as acetylcholine (4). Wall shear stress (WSS) has also been found to regulate the activity and expression of eNOS (34,40).Oscillatory and reverse WSS have negative effects on the endothelium due to superoxide (O 2 Ϫ ) production (14, 27, 28, 36, 52). It has been found that reverse flow in blood vessels causes reduced NO due to increased O 2 Ϫ production (36). Since NO is atheroprotective, regions of oscillatory and reverse WSS are more prone to atherosclerosis. Regions near branch points and curved vessels produce near-wall reverse flow (15,16).O 2 Ϫ can quickly inactivate NO, causing reduced NO bioavailability and endothelial dysfunction (9, 33). This endothelial dysfunction is implicated in atherosclerosis, hypertension, and heart failure (9,13,14,18,21). Reduced NO in the vessel wall impairs endothelium-dependent vasodilation, decreases inhibition of platelet and leukocyte adhesion, and is linked to the development of intimal hyperplasia (4, 21, 51). Our group has previously shown that NO production is reduced during reverse flow and that the addition of Tempol (an O 2 Ϫ scavenger) restored NO production in reverse flow to...

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“…Lipopolysaccharide (LPS), a constituent of the outer membrane of gram-negative bacteria, primes activation of the phagocytic NOX2 enzyme. In guinea pigs, LPS-stimulated ROS generation by neutrophils and ALI were significantly reduced with apocynin, a putative inhibitor of NOX2 (136,140). Emerging evidence suggests the presence of crosstalk between NOX enzymes and Toll-like receptors (TLRs), which cooperatively participate in the host innate immune response.…”

Section: Nox Enzymes In Acute Lung Injurymentioning

confidence: 99%

NOX Enzymes and Pulmonary Disease

Griffith

Pendyala²,

Hecker³

et al. 2009

Antioxidants & Redox Signaling

133

112

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The primary function of the lung is to facilitate the transfer of molecular oxygen (O 2 ; dioxygen) from the atmosphere to the systemic circulation. In addition to its essential role in aerobic metabolism, O 2 serves as the physiologic terminal acceptor of electron transfer catalyzed by the NADPH oxidase (NOX) family of oxidoreductases. The evolution of the lungs and circulatory systems in vertebrates was accompanied by increasing diversification of NOX family enzymes, suggesting adaptive roles for NOX-derived reactive oxygen species in normal physiology. However, this adaptation may paradoxically carry detrimental consequences in the setting of overwhelming=persistent environmental stressors, both infectious and noninfectious, and during the process of aging. Here, we review current understanding of NOX enzymes in normal lung physiology and their pathophysiologic roles in a number of pulmonary diseases, including lung infections, acute lung injury, pulmonary arterial hypertension, obstructive lung disorders, fibrotic lung disease, and lung cancer. Antioxid. Redox Signal. 11, 2505-2516.

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Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells

Cited by 152 publications

References 21 publications

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

NADPH oxidase has a directional response to shear stress

NOX Enzymes and Pulmonary Disease

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