Impaired production of nitric oxide, superoxide, and hydrogen peroxide in glucose 6-phosphate-dehydrogenase-deficient granulocytes.
Since the generation of superoxide and hydrogen peroxide by NADPH oxidase and nitric oxide (NO) by NO synthase (NOS) in granulocytes is NADPH-dependent, we investigated the production of NO, superoxide and H2O2 in glucose 6-phosphate dehydrogenase (G6PD)-deficient human granulocytes. Our results showed that upon stimulation with either 5 microg/ml of lipopolysaccharide (LPS) or 10 microM of phorbol 12-myristate 13-acetate (PMA), the production of nitrite in normal granulocytes was elevated, 252 +/- 135% and 239 +/- 72%, respectively, compared to the resting stage. In contrast, G6PD-deficient granulocytes did not produce more nitrite upon stimulation with either LPS or PMA compared to the resting stage. Western blot analysis indicated a normal expression pattern of inducible NOS in G6PD-deficient granulocytes. In addition, the production of H2O2 and superoxide was also significantly impaired in G6PD-deficient granulocytes compared to control cells. These data demonstrate that G6PD deficiency causes an impairment in the production of NO, superoxide and H2O2.
Tsai
K J
KJ
Graduate Institute of Basic Medical Sciences and School of Medical Technology, Chang Gung University, Tao-yuan, Taiwan.
Hung
I J
IJ
Chow
C K
CK
Stern
A
A
Chao
S S
SS
Chiu
D T
DT
D004912:Erythrocytes / Q000201:enzymology; D005954:Glucosephosphate Dehydrogenase / Q000097:blood*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000201:enzymology; D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000097:blood; D052247:Nitric Oxide Synthase Type II; D012016:Reference Values; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008070:Lipopolysaccharides; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D013755:Tetradecanoylphorbol Acetate