Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei Province, P. R. China.
Bioreactor and Protein Drug Research and Development Center of Hebei Universities, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei Province, P. R. China.
J Cell Biochem. 2018 Jul;119(7):5517-5527. doi: 10.1002/jcb.26715. Epub 2018 Apr 6.
Elevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron-regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1-adrenergic receptor agonist), prazosin (PZ, α1-adrenergic receptor antagonist), and/or propranolol (Pro, β-adrenergic receptor antagonist). The levels of hepcidin, as well as signal transducer and activator of transcription 3 (STAT3), ferroportin 1 (FPN1), and ferritin-light (Ft-L) protein in the liver or spleen, were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were treated with AD or NE continuously for 7 days, an increase in hepatic hepcidin mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the expected downstream effects of elevated hepcidin, namely decreased FPN1 expression and increased Ft-L protein and non-heme iron concentrations in the spleen, were observed after the continuous AD or NE treatments. Taken together, we found that AD or NE increase hepatic hepcidin expression via the α1-adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin decreased FPN1 levels in the spleen, likely causing the increased iron accumulation in the spleen.
铁储存升高与高血压进展有关，而高血压与患者血浆儿茶酚胺水平升高有关。然而，我们对儿茶酚胺与铁调节之间的联系了解有限。铁调素是一种关键的铁调节激素，可维持体内铁平衡。在本研究中，我们研究了肾上腺素（AD）和去甲肾上腺素（NE）对肝脏铁调素调节的影响。用 AD、NE、苯肾上腺素（PE，α1-肾上腺素受体激动剂）、哌唑嗪（PZ，α1-肾上腺素受体拮抗剂）和/或普萘洛尔（Pro，β-肾上腺素受体拮抗剂）处理小鼠。评估了肝脏或脾脏中铁调素、信号转导和转录激活因子 3（STAT3）、亚铁转运蛋白 1（FPN1）和铁蛋白轻链（Ft-L）蛋白的水平。AD、NE 或 PE 处理 6 小时后，肝内铁调素 mRNA 水平增加。用 PZ 预处理，但不用 Pro 预处理，可消除 AD 或 NE 对 STAT3 磷酸化和肝内铁调素表达的影响。当连续 7 天用 AD 或 NE 处理小鼠时，也观察到肝内铁调素 mRNA 水平和血清铁调素浓度增加。同时，在连续 AD 或 NE 处理后，观察到升高的铁调素的预期下游效应，即 FPN1 表达降低和脾内 Ft-L 蛋白和非血红素铁浓度增加。综上所述，我们发现 AD 或 NE 通过α1-肾上腺素受体和 STAT3 通路增加了小鼠肝脏铁调素的表达。升高的肝铁调素降低了脾内的 FPN1 水平，可能导致脾内铁蓄积增加。
