Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase.
Although glial cells play a major role in the pathogenesis of many neurological diseases by exacerbating neuronal and non-neuronal cell death, the mechanisms involved are unclear. We examined the effects of microglia-(MCM) or astrocyte-(ACM) conditioned media obtained by chemical ischemia on the neuronal injury in SH-SY5Y cells. Chemical ischemia was induced by the treatment with NaN(3) and 2-deoxy-d-glucose for 2h. MCM-treated SH-SY5Y cells showed reduced the viability, increased caspase-3 activity, decreased Bcl-2/Bax ratio, and increased cytochrome c release, increased inflammatory cytokines, and increased reactive oxygen species (ROS) generation. MCM also increased gp91phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which was inhibited by NADPH oxidase inhibitor, apocynin, and gp91phox siRNA. However, ACM did not show any significant changes. The results suggest that microglia activated by ischemic insult may increase reactive oxygen species generation via activation of gp91phox NADPH oxidase, resulting in neuronal injury.
Hur
Jinyoung
J
Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea.
Lee
Pyeongjae
P
Kim
Mi Jung
MJ
Kim
Younghoon
Y
Cho
Young-Wuk
YW
D017209:Apoptosis; D001253:Astrocytes / Q000201:enzymology; D002545:Brain Ischemia / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003847:Deoxyglucose / Q000633:toxicity; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D017628:Microglia / Q000201:enzymology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019810:Sodium Azide / Q000633:toxicity
D017077:Culture Media, Conditioned; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D019810:Sodium Azide; D003847:Deoxyglucose; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases