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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Increased inducible nitric oxide synthase protein but limited nitric oxide formation occurs in astrocytes of the hph-1 (tetrahydrobiopterin deficient) mouse.

It has been suggested that decreased tetrahydrobiopterin (BH4) availability may be a useful tool for limiting excessive nitric oxide (NO) formation. In order to test this hypothesis we utilised cultured astrocytes derived from the brain of the hph-1 (BH4 deficient) mouse. In response to treatment with lipopolysaccharide and interferon-gamma (LPS/gammaIFN) levels of BH4 doubled in both wild type and hph-1 astrocytes. However, levels of BH4 in hph-1 astrocytes remained only 25% of the wild type astrocytes. Nitric oxide formation, measured with an NO-electrode, was 45% less from LPS/gammaIFN stimulated hph-1 astrocytes compared with wild type stimulated astrocytes. In contrast, iNOS specific activity and iNOS protein were enhanced in hph-1 stimulated astrocytes by 40 and 60%, respectively when compared with wild type. In conclusion it appears that whilst a decrease in BH4 may limit NO release per se, the possibility and consequences of long term 'over' induction of iNOS protein requires further consideration.[1]

References

  1. Increased inducible nitric oxide synthase protein but limited nitric oxide formation occurs in astrocytes of the hph-1 (tetrahydrobiopterin deficient) mouse. Barker, J.E., Strangward, H.M., Brand, M.P., Hurst, R.D., Land, J.M., Clark, J.B., Heales, S.J. Brain Res. (1998) [Pubmed]
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