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

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Tetrahydrobiopterin modulates cyclooxygenase-2 expression in human mesangial cells.

Tetrahydrobiopterin (BH4) biosynthetic pathways are stimulated under inflammatory conditions. The newly synthesized BH4 serves as a cofactor for optimal activity of inducible nitric oxide synthase (NOS2). In human mesangial cells (HMC), BH4 is also a limiting factor for NOS2 expression. In this study we show that BH4 availability can also play a modulatory role in the expression of cyclooxygenase 2 ( COX-2) in HMC. Supplementing HMC with the BH4 donor sepiapterin potentiated IL-1beta/TNF-alpha- induced COX-2 expression by approximately 2-fold. This effect was abolished by methotrexate. In contrast, the NOS inhibitor L-NAME and the soluble guanylate cyclase inhibitor ODQ did not block sepiapterin amplification of COX-2 expression. Moreover, sepiapterin was found to modulate the tyrosine phosphorylation of several cellular substrates, an early event which occurred well before the induction of NOS2 could be evidenced. These findings suggest a role for BH4 in the modulation of mesangial cell responses to pro-inflammatory stimuli.[1]

References

  1. Tetrahydrobiopterin modulates cyclooxygenase-2 expression in human mesangial cells. Pérez-Sala, D., Díaz-Cazorla, M., Ros, J., Jiménez, W., Lamas, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
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