Aluminum Chloride- and Norepinephrine-Induced Immunotoxicity on Splenic Lymphocytes by Activating β2-AR/cAMP/PKA/NF-κB Signal Pathway in Rats
2014
Xiu, Chunyu | Ren, Limin | Li, Miao | Liu, Shiming | Zhu, Yanzhu | Liu, Jianyu | Li, Yanfei
We found in our previous research that aluminum (Al) exposure induced immunotoxicity on spleen and increased norepinephrine (NE) content in serum from rats. However, it is unclear how NE is involved in the AlCl₃immunotoxicity on rats. Therefore, this experiment was designed to explore the mechanism of AlCl₃and NE-induced immunotoxicity on the splenic lymphocytes. Eighty male Wistar rats were orally exposed to AlCl₃(0, 64, 128, and 256 mg/kg BW) through drinking water for 120 days. Al contents in brain and spleen; NE contents in serum and in the hypothalamus; β₂-AR density; cAMP content; β₂-AR, PKA, and NF-κB mRNA expression levels; and protein expressions of PKA and nuclear NF-κB in splenic lymphocytes of AlCl₃-treated rats were examined. The results showed that AlCl₃increased NE content in serum, the β₂-AR density, the β₂-AR and PKA (C-subunits) mRNA expression levels, cAMP content and the PKA (C-subunits) protein expression levels in lymphocytes, whereas, decreased NE content in the hypothalamus, the NF-κB (p65) mRNA expression level and nuclear NF-κB (p65) protein expression level in lymphocytes. These results indicated that the accumulated AlCl₃in spleen and the increased NE in serum induced the immunotoxicity on splenic lymphocytes by activating β₂-AR/cAMP/PKA/NF-κB signal pathway in rats.
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