Control of JNK for an activation of NADPH oxidase in LPS-stimulated BV2 microglia.
Summary of "Control of JNK for an activation of NADPH oxidase in LPS-stimulated BV2 microglia."
NADPH oxidase is a main regulator for H(2)O(2) productivity in neuroinflammatory cells, including microglia, under various CNS diseases and its activity is controlled by mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK). However, little is known about the link between NADPH oxidase-driven H(2)O(2) productivity and JNK in microglia. The purpose of this study is to uncover the link using lipopolysaccharide (LPS)-stimulated BV2 microglia. LPS-stimulated BV2 microglia produced H(2)O(2) that was decreased by NADPH oxidase inhibitors, including 4-(2-aminoethyl)benzenesulfonylfluoride and diphenyleneiodonium chloride. In addition, NADPH oxidase was activated in LPS-stimulated BV2 cells. These results suggest that NAPDH oxidase is a main factor for H(2)O(2) productivity in LPS-stimulated BV2 microglia. Based on a semi-quantitative PCR analysis, two of NADPH oxidase components, p47(phox) and gp91(phox), were involved in the activation of NADPH oxidase because transcriptional levels of both components were upregulated by LPS. Role of JNK in NADPH oxidase-regulated H(2)O(2) productivity was pursued using specific inhibitors, including SP600125 and JNK inhibitory peptide (JIP). Inhibition of the JNK pathways significantly reduced H(2)O(2) productivity, which was closely related to the attenuation of NADPH oxidase activation and the upregulation of components. We conclude that JNK pathways are involved in NADPH oxidase-mediated H(2)O(2) productivity in BV2 microglia.
Department of Pharmacology, College of Pharmacy, Gachon University of Medicine and Science, Incheon, 406-799, Korea.
This article was published in the following journal.
Name: Archives of pharmacal research
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22553064
- DOI: http://dx.doi.org/10.1007/s12272-012-0415-1
Medical and Biotech [MESH] Definitions
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (GRANULOMATOUS DISEASE, CHRONIC) often die as a result of recurrent bacterial infections.
Sulfite Reductase (nadph)
A NADPH-dependent oxidase that reduces hydrogen sulfite to HYDROGEN SULFIDE. It is found in many microoganisms.
Rac1 Gtp-binding Protein
A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 126.96.36.199.
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