Tetrahydrobiopterin attenuates superoxide-induced reduction in nitric oxide. Academic Article uri icon

abstract

  • NADPH oxidase, a source of superoxide anion (O2(-)), can be stimulated by oxidized low-density lipoprotein (OxLDL). We examined whether tetrahydrobiopterin (BH4) could reduce OxLDL-induced O2(-) production by NADPH oxidase, increasing nitric oxide (NO) synthesis. Endothelial cells incubated with OxLDL produced more O2(-) (35-67%) than untreated cells, with the highest increase 1 hour after OxLDL addition. The elevated O2(-) production correlated with the translocation of the p47phox subunit of NADPH oxidase from the cytosol to the membrane. Cells exhibited a marked decrease in both BH4 (83 per cent) and NO (54 per cent) in the same hour following exposure to OxLDL. An NADPH oxidase inhibitor, apocynin, or antioxidant, N-acetyl-L-cysteine, substantially attenuated the reduction in both BH4 and NO. The O2(-) production was increased when cells were pretreated with an inhibitor of BH4 synthesis and decreased following pretreatment with a BH4 precursor, suggesting that NADPH oxidase-induced imbalance of endothelial NO and O2(-) production can be modulated by BH4 concentrations. BH4 may be critical in combating oxidative stress, restoring proper redox state, and reducing risk for cardiovascular disease including atherosclerosis.

published proceedings

  • Front Biosci (Schol Ed)

author list (cited authors)

  • Bowers, M. C., Hargrove, L. A., Kelly, K. A., Wu, G., & Meininger, C. J.

citation count

  • 5

complete list of authors

  • Bowers, Mark C||Hargrove, Laura A||Kelly, Katherine A||Wu, Guoyao||Meininger, Cynthia J

publication date

  • June 2011