Change in expression of the guanosine triphosphate cyclohydrolase I in LPS-stimulated rats is tissue specific

Background: The synthesis of tetrahydrobiopterin (BH4), a necessary cofactor for inducible nitric oxide synthase (iNOS), has been reported to be controlled by guanosine triphosphate cyclohydrolase I (GTPCH). Previous studies have demonstrated that GTPCH was induced by bacterial toxin. However, in a study using lipopolysaccharide (LPS)-treated murine macrophages model, we found that GTPCH expression was in fact constitutive rather than inducible. To further elucidate the effects of endotoxemia on GTPCH expression, we therefore preformed this LPS-treated rodent endotoxemia study with special focus on lung, liver, and kidney. Methods: Rats randomly received either normal saline (N/S) or LPS injection. At five different time points (0, 1, 2, 3 and 4 h after LPS injection in LPS group and comparable time points in N/S group), four rats from each group were sacrificed. Snap frozen tissues were then analyzed using semi-quantitative RT-PCR to determine GTPCH mRNA concentrations. Results: GTPCH mRNA concentrations in lung and liver tissues were similar between groups. On the other hand, GTPCH mRNA concentrations in renal tissues were significantly higher in the LPS group as compared with the N/S group. Our data demonstrated that GTPCH expression in lung and liver tissues was constitutive rather than inducible, whereas renal GTPCH expression was induced by LPS in a time-dependent manner. Conclusions: GTPCH expression is tissue specific. Different tissues react differently to endotoxemia in terms of GTPCH expression. Therefore, efforts aiming at modulating GTPCH expression to limit NO overproduction should adjust accordingly.