Transglutaminase 2 induces nitric oxide synthesis in BV-2 microglia.
A hallmark of brain inflammation is the activation of microglia. Excessive production of nitric oxide (NO), as a consequence of increased inducible nitric oxide synthase (iNOS) in glia, contributes to neurodegeneration. Transglutaminase 2 (TGase 2) is a cross-linking enzyme, which is increased in neurodegeneration. TGase 2 is also considered to be a useful and reliable marker for activation levels in resident and inflammatory macrophages. Therefore, an increase of TGase 2 expression may contribute to activation of microglia. To test this hypothesis, we analyzed the expression of TGase 2 in BV-2 microglia activated with lipopolysaccharide (LPS). Total TGase activity was increased about 5-fold after 24h exposure to LPS. The increase of NO synthesis is correlated with increase of TGase 2 expression. Secretion of NO was reduced between 40 and 80% by TGase inhibition in a dose-dependent manner. This suggests that TGase 2 appears to control iNOS transcription.
Park
Key Chung
KC
Department of Neurology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Chung
Kyung Cheon
KC
Kim
Yoon-Seong
YS
Lee
Jongmin
J
Joh
Tong H
TH
Kim
Soo-Youl
SY
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007210:Indoleacetic Acids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007210:Indoleacetic Acids; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C030737:indoleacetic acid; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins