| Formaldehyde (FA) is a well-known indoor air pollution. In recent years, the causal relationship between FA exposure and leukemia attracts more and more attentions. Although the U.S. National Toxicology Program (NTP) has classified FA as human leukemogen, FA increases susceptibility to leukemogenesis and the possible molecular mechanisms involved remain to be elucidated. As an endogenous substance, FA has an independent metabolic pathway and can regulate other metabolic reactions, which is similar as the small gaseous signal molecular. Thereby, we put forward the hypothesis that FA could regulate the function of body through the signal transduction pathway as a signal molecule. Although FA exposure did not increase the total FA concentrations in organism, it can interfere with the normal physiological function by regulating the corresponding signal molecular pathways, and even lead to the organic lesion. Therefore, this article aimed to explore whether FA has an effect on metabolic regulation of hematopoietic system via the signaling pathway with the key point of NO/cGMP and cAMP signaling pathways.In this study,32 BALB/c male mice were selected and divided into 4 groups, with 8 mice in each group:control group,0.5 mg/m3 FA exposure group,3.0 mg/m3 FA exposure group and NG-monomethyl-L-arginine (L-NMMA) group. The mice of L-NMMA group were injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/kg) and exposed to 3.0 mg/m3 FA. In the present study mice were exposed to FA via systemic exposure 8 h per day (9 a.m.-5 p.m.) for 7 days. After FA exposure, the concentrations of nitric oxide synthase (NOS), nitric oxide (NO), cyclic adenosine monophosphate (cAMP), and cyclic guanine monophosphate (cGMP) in bone marrow, plasma, cerebral cortex, hippocampus and brain stem were determined; the mRNA level of the protein kinase A (PKA), protein kinases G (PKG) and cAMP-response element binding protein (CREB) were detected; the slices of brain tissue were also examined.The results showed that FA exposure has an varying effect in NO/cGMP and cAMP signaling pathways. The levels of different molecules in NO/cGMP signaling pathway were measured,the concentrations of NOS, NO and cGMP in bone marrow, plasma and different brain regions appeared significant difference under different concentrations of FA exposure, and the expression of PKG increased significantly, but the biochemical indexes of mice in L-NMMA group had different degrees of recovery. The cAMP signaling pathway in plasma, bone marrow and different brain regions were also affected. The cAMP contents in plasma and different brain regions were significantly increased with 0.5 mg/m3 FA exposure and then decreased at 3.0 mg/m3, the expression of the PKA and CREB increased significantly, but the mice injected with L-NMMA has been less affected by FA exposure compare with 3.0 mg/m3 FA exposure group. A number of apoptotic neuronal cells were observed in 3.0 mg/m3 FA exposure group through histopathological examination. However, FA exposure caused less damage to the neuronal cells in the L-NMMA group compared with the 3.0 mg/m3 FA exposed group.These results indicated that inhaled FA exposure had an adverse effect on the normal physiological function of NO/cGMP and cAMP signaling pathways, in addition, the toxic effect on mice induced by inhalation FA could be alleviated by injection with L-NMMA. We also found that the changes of different molecules in the signal pathway were similar as the symptoms of leukemia patients. These conclusions provided a new research approach to explore the pathogenesis of leukemia induced by FA exposure, we can take the signal pathway as the breakthrough point to study the changes of leukemia related genes in depth, and then to find the biological evidences whether leukemia could be induced by FA exposure. |
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