Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: Implication of NADPH oxidase
| Autor: | Juliana Hwang, Bernard Lassègue, Tzung K. Hsiai, Alex Sevanian, Laura Marcu, Roza E. Clempus, Mahsa Rouhanizadeh |
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| Rok vydání: | 2005 |
| Předmět: |
Down-Regulation
Pentose phosphate pathway Biochemistry Article chemistry.chemical_compound Superoxides Physiology (medical) Animals Cells Cultured chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology Superoxide NADPH Oxidases NOX4 Glutathione Molecular biology Up-Regulation Spectrometry Fluorescence Matrix Metalloproteinase 9 chemistry NAD(P)H oxidase Apocynin Phosphatidylcholines biology.protein Matrix Metalloproteinase 2 Cattle Endothelium Vascular NADP |
| Zdroj: | Free Radical Biology and Medicine. 39:1512-1522 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2005.07.013 |
| Popis: | 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, ox-PAPC + apocynin = 21.17 ± 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. |
| Databáze: | OpenAIRE |
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