Glucosamine exerts a neuroprotective effect via suppression of inflammation in rat brain ischemia/reperfusion injury.
We investigated the neuroprotective effect of glucosamine (GlcN) in a rat middle cerebral artery occlusion model. At the highest dose used, intraperitoneal GlcN reduced infarct volume to 14.3% ± 7.4% that of untreated controls and afforded a reduction in motor impairment and neurological deficits. Neuroprotective effects were not reproduced by other amine sugars or acetylated-GlcN, and GlcN suppressed postischemic microglial activation. Moreover, GlcN suppressed lipopolysaccharide (LPS)-induced upregulation of proinflammatory mediators both in vivo and in culture systems using microglial or macrophage cells. The anti-inflammatory effects of GlcN were mainly attributable to its ability to inhibit nuclear factor kappaB (NF-κB) activation. GlcN inhibited LPS-induced nuclear translocation and DNA binding of p65 to both NF-κB consensus sequence and NF-κB binding sequence of inducible nitric oxide synthase promoter. In addition, we found that GlcN strongly repressed p65 transactivation in BV2 cells using Gal4-p65 chimeras system. P65 displayed increased O-GlcNAcylation in response to LPS; this effect was also reversed by GlcN. The LPS-induced increase in p65 O-GlcNAcylation was paralleled by an increase in interaction with O-GlcNAc transferase, which was reversed by GlcN. Finally, our results suggest that GlcN or its derivatives may serve as novel neuroprotective or anti-inflammatory agents.
Hwang
So-Young
SY
Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, South Korea.
Shin
Joo-Hyun
JH
Hwang
Ji-Sun
JS
Kim
Song-Yi
SY
Shin
Jin-A
JA
Oh
Eok-Soo
ES
Oh
Seikwan
S
Kim
Jung-Bin
JB
Lee
Ja-Kyung
JK
Han
Inn-Oc
IO
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005944:Glucosamine / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012720:Severity of Illness Index; D013778:Tetrazolium Salts; D014162:Transfection / Q000379:methods
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D005944:Glucosamine