NADPH oxidase and nitric oxide synthase-dependent superoxide production is increased in proliferative lupus nephritis

ABSTRACT The Brucella abortus virB locus is required for establishing chronic infection in the mouse. Using in vitro and in vivo models, we investigated whether virB is involved in evasion of the bactericidal activity of NADPH oxidase and the inducible nitric oxide synthase (iNOS) in macrophages. Elimination of NADPH oxidase or iNOS activity in macrophages in vitro increased recovery of wild-type B. abortus but not recovery of a virB mutant. In mice lacking either NADPH oxidase or iNOS, however, B. abortus infected and persisted to the same extent as it did in congenic C57BL/6 mice up until 60 days postinfection, suggesting that these host defense mechanisms are not critical for limiting bacterial growth in the mouse. A virB mutant did not exhibit increased survival in either of the knockout mouse strains, indicating that this locus does not contribute to evasion of nitrosative or oxidative killing mechanisms in vivo.

Download Full-text

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with the development of lupus nephritis

Lupus ◽

10.1191/0961203304lu516oa ◽

2004 ◽

Vol 13 (3) ◽

pp. 188-191 ◽

Cited By ~ 15

Author(s):

Y H Lee ◽

H J Kim ◽

Y H Rho ◽

S J Choi ◽

J D Ji ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Lupus Nephritis ◽

Endothelial Nitric Oxide Synthase ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Intron 4

Download Full-text

Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00935.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. H2167-H2172 ◽

Cited By ~ 85

Author(s):

Mathew Eric Hyndman ◽

Subodh Verma ◽

Robin J. Rosenfeld ◽

Todd J. Anderson ◽

Howard G. Parsons

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Endothelial Function ◽

Active Site ◽

Superoxide Production ◽

Oxide Synthase

The present study was designed to investigate the interaction between 5-methyltetrahydrofolate and tetrahydrobiopterin in modulating endothelial function. Tetrahydrobiopterin is a critical cofactor for nitric oxide synthase and maintains this enzyme as a nitric oxide- versus superoxide-producing enzyme. The structure of 5-methyltetrahydrofolate is similar to tetrahydrobiopterin and both agents have been shown to improve endothelium-dependent vasodilatation. We hypothesized that 5-methyltetrahydrofolate interacts with nitric oxide synthase in a fashion analogous, yet independent, of tetrahydrobiopterin to improve endothelial function. We demonstrate that 5-methyltetrahydrofolate binds the active site of nitric oxide synthase and mimics the orientation of tetrahydrobiopterin. Furthermore, 5-methyltetrahydrofolate attenuates superoxide production (induced by inhibition of tetrahydrobiopterin synthesis) and improves endothelial function in aortae isolated from tetrahydrobiopterin-deficient rats. We suggest that 5-methyltetrahydrofolate directly interacts with nitric oxide synthase to promote nitric oxide (vs. superoxide) production and improve endothelial function. 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability.

Download Full-text