Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury

Dodd‐o, Jeffrey M.; Pearse, David B.

doi:10.1152/ajpheart.2000.279.1.h303

Cited by 106 publications

(89 citation statements)

References 43 publications

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“…This botanical compound is derived from the root of Picrorhiza kurroa (Dodd-O and Pearse, 2000) and has been used as a Chinese medicinal herb for treatment of a number of infectious and inflammatory diseases (Hougee et al, 2006;Kim-Mitsuyama et al, 2005;Lafeber et al, 1999). Studies from our laboratory showed the ability for apocynin to protect against delayed neuronal death induced by global cerebral ischemia in the gerbil .…”

Section: Discussionmentioning

confidence: 96%

“…Apocynin is a methoxy-substituted catechol extracted from the root of Picrorhiza kurroa plant. This compound has been shown to block translocation of the cytosolic subunits to the membrane (Dodd-O and Pearse, 2000). DPI is not a selective inhibitor of NADPH oxidase as it can also inhibit electron transport through the cytochrome b (O'Donnell et al, 1993) as well as other redox cycling reactions.…”

Section: Paraquat-induced Ros Is Linked To Activation Of Nadph Oxidasementioning

confidence: 99%

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Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Miller

Sun

2007

Brain Research

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Excess production of reactive oxygen species (ROS) is an important mechanism underlying the pathogenesis of a number of neurodegenerative diseases including Parkinson's disease (PD) which is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Exposure to paraquat, an herbicide with structure similar to the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP + ), has been shown to produce PD-like symptoms. Despite previous focus on the dopaminergic neurons and signaling pathways involved in their cell death, recent studies have implicated microglial cells as a major producer of ROS for damaging neighboring neurons. In this study, we examined the source of ROS and the underlying signaling pathway for paraquat-induced cytotoxicity to BV-2 microglial cells. Paraquat-induced ROS production (including superoxide anions) in BV-2 cells was accompanied by translocation of the p67phox cytosolic subunit of NADPH oxidase to the membrane. Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. Apocynin and DPI also rescued cells from paraquat-induced toxicity. The inhibitors for protein kinase C delta (PKCδ) or extracellular signal-regulated kinases (ERK1/2) could partially attenuate paraquat-induced ROS production and cell death. Rottlerin, a selective PKCδ inhibitor, also inhibited paraquat-induced translocation of p67phox. Taken together, this study demonstrates the involvement of ROS from NADPH oxidase in mediating paraquat cytotoxicity in BV-2 microglial cells and this process is mediated through PKCδ-and ERK-dependent pathways.

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Section: Discussionmentioning

confidence: 96%

Section: Paraquat-induced Ros Is Linked To Activation Of Nadph Oxidasementioning

confidence: 99%

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Miller

Sun

2007

Brain Research

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“…The formation of O 2 −• by the endothelial NADPH oxidase accounts for the reduced NO bioavailability, development of endothelial dysfunction from the aortic ring of gp91phox-knockout mice (gp91phox−/−) [50]. In this context, apocynin (4-hydroxy-3-methoxyacetophenonone) has been demonstrate to act as a potent and selective inhibitor of NADPH oxidase system in both in vitro and animal models [51][52][53] by interfering with the translocation of an essential cytosolic protein, p47phox [54][55][56]. Diphenylene iodonium (DPI) nonspecifically inhibits flavoprotein-containing enzymes, including NADPH oxidases, NOS, and complex I of mitochondrial electron transport chain [57].…”

Section: Discussionmentioning

confidence: 99%

Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: Implication of NADPH oxidase

Rouhanizadeh

Hwang

Clempus

et al. 2005

Free Radical Biology and Medicine

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Modified low-density lipoprotein (LDL) induces reactive oxygen species (ROS) production by vascular cells. It is unknown if specific oxidized components in these LDL particles such as oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) can stimulate ROS production. Bovine aortic endothelial cells (BAEC) were incubated with ox-PAPC (50 μg/ml). At 4 h, ox-PAPC significantly enhanced the rate of O 2 −• production. Pretreatment of BAEC in glucose-free Dulbecco's modified Eagle's medium plus 10 mM 2-deoxyglucose (2-DOG), the latter being an antimetabolite that blocks NADPH production by the pentose shunt, significantly reduced the rate of O 2 −• production. The intensity of NAD(P)H autofluorescence decreased by 28 ± 12% in BAEC incubated with ox-PAPC compared to untreated cells, with a further decrease in the presence of 2-DOG. Ox-PAPC also increased Nox4 mRNA expression by 2.4-fold ± 0.1 while pretreatment of BAEC with the small interfering RNA (siNox4) attenuated Nox4 RNA expression. Ox-PAPC further reduced the level of glutathione while pretreatment with apocynin (100 μM) restored the GSH level (control = 22.54 ± 0.23, GSH = 18.06 ± 0.98, apocynin = 22.55 ± 0.60,.17 ± 0.36 nmol/10 6 cells). Treatment with ox-PAPC also increased MMP-2 mRNA expression accompanied by a 1.5-fold increase in MMP-2 activity. Ox-PAPC induced vascular endothelial O 2 −• production that appears to be mediated largely by NADPH oxidase activity.

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“…2 However, the molecular and cellular mechanisms that are responsible for the development of COPD are not well understood. Cigarette smoke (CS) contains an estimated 10 15 to 10 17 oxidants/free radicals and ϳ4700 different chemical compounds, including reactive aldehydes, quinones, and semiquinones, per puff. 3,4 It has been shown that CS is the major risk factor for the development of COPD, and that chronic exposure to CS leads to lung inflammation with an increase of inflammatory cells, such as macrophages, neutrophils, dendritic cells, and CD8 ϩ T lymphocytes.…”

Section: Cigarette Smoke (Cs) Induces Recruitment Of Inflammatory Celmentioning

confidence: 99%

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Yao

Edirisinghe

Yang

et al. 2008

The American Journal of Pathology

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Cigarette smoke (CS) induces recruitment of inflammatory cells in the lungs leading to the generation of reactive oxygen species (ROS), which are involved in lung inflammation and injury. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a multimeric system that is responsible for ROS production in mammalian cells. We hypothesized that NADPH oxidase-derived ROS play an important role in lung inflammation and injury and that targeted ablation of components of NADPH oxidase (p47 phox and gp91 phox ) would protect lungs against the detrimental effects of CS. To test this hypothesis, we exposed p47 phox؊/؊ and gp91 phox؊/؊ mice to CS and examined inflammatory response and injury in the lung. Surprisingly, although CS-induced ROS production was decreased in the lungs of p47 phox؊/؊ and gp91 phox؊/؊ mice compared with wild-type mice, the inflammatory response was significantly increased and was accompanied by development of distal airspace enlargement and alveolar destruction. This pathological abnormality was associated with enhanced activation of the TLR4-nuclear factor-B pathway in response to CS exposure in p47 phox؊/؊ and gp91 phox؊/؊ mice. This phenomenon was confirmed by in vitro studies in which treatment of peritoneal macrophages with a nuclear factor-B inhibitor reversed the CS-induced release of proinflammatory mediators. Thus, these data suggest that genetic ablation of components of NADPH oxidase enhances susceptibility to the proinflammatory effects of CS leading to airspace enlargement and alveolar damage.

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Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury

Cited by 106 publications

References 43 publications

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: Implication of NADPH oxidase

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

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