The mammalian neuroendocrine hormone norepinephrine supplies iron for bacterial growth in the presence of transferrin or lactoferrin
The mammalian neuroendocrine hormone norepinephrine supplies iron for bacterial growth in the presence of transferrin or lactoferrin
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DOI：
10.1128/jb.182.21.6091-6098.2000
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发表时间：
2000-11-01
影响因子：
3.2
通讯作者：
Williams, PH
中科院分区：
文献类型：
--
作者：
Freestone, PPE;Lyte, M;Williams, PH
去甲肾上腺素能刺激一系列细菌在营养不良的SAPI最低盐中生长，SAPI最低盐中含有30%的血清。在SAPI培养液中加入不同大小的血清成分表明，转铁蛋白是去甲肾上腺素刺激大肠杆菌生长所必需的，由于血清对转铁蛋白的抑菌主要是由于转铁蛋白对铁的抑制能力，我们认为去甲肾上腺素可以通过提供转铁蛋白结合铁来克服这种影响，去甲肾上腺素刺激血清-SAPI培养基中刺激细菌生长的去甲肾上腺素浓度导致铁饱和的转铁蛋白的结合铁丢失，变性凝胶中出现单铁和脱铁异构体。去甲肾上腺素也会导致乳铁蛋白中铁的损失。相比之下，药理不活跃的代谢物去甲肾上腺素3-O-硫酸盐不会导致转铁蛋白或乳铁蛋白的铁损失，也不会刺激血清SAPI培养上清液中的细菌生长。去甲肾上腺素与转铁蛋白、乳铁蛋白和血清白蛋白形成稳定的络合物。去甲肾上腺素-转铁蛋白和去甲肾上腺素-乳铁蛋白复合体，而不是去甲肾上腺素-载脂蛋白或去甲肾上腺素-白蛋白复合体，在没有额外去甲肾上腺素的情况下，促进了血清-SAPI上清液中细菌的生长。去甲肾上腺素刺激细菌细胞在含有铁-55和转铁蛋白或乳铁蛋白络合物的培养液中生长，导致细菌细胞摄取放射性。此外，在含有[H-3]去甲肾上腺素的培养液中，去甲肾上腺素刺激的生长表明伴随着去甲肾上腺素的摄取。在每种情况下，添加过量的铁都不会影响生长，但显著降低了与细菌细胞相关的放射性水平(Fe-55或H-3)。儿茶酚胺介导的铁供应在感染性疾病的病理生理中的作用被提出。
Norepinephrine stimulates the growth of a range of bacterial species in nutritionally poor SAPI minimal salts medium containing 30% serum. Addition of size-fractionated serum components to SAPI medium indicated that transferrin was required for norepinephrine stimulation of growth of Escherichia coli, Since bacteriostasis by serum is primarily due to the iron-withholding capacity of transferrin, we considered the possibility that norepinephrine can overcome this effect by supplying transferrin-bound iron for growth, Incubation with concentrations of norepinephrine that stimulated bacterial growth in serum-SAPI medium resulted in loss of bound iron from iron-saturated transferrin, as indicated by the appearance of monoferric and apo-isoforms upon electrophoresis in denaturing gels. Norepinephrine also caused the loss of iron from lactoferrin. The pharmacologically inactive metabolite norepinephrine 3-O-sulfate, by contrast, did not result in iron loss from transferrin or lactoferrin and did not stimulate bacterial growth in serum-SAPI medium. Norepinephrine formed stable complexes with transferrin, lactoferrin, and serum albumin. Norepinephrine-transferrin and norepinephrine-lactoferrin complexes, but not norepinephrine-apotransferrin or norepinephrine-albumin complexes, stimulated bacterial growth in serum-SAPI medium in the absence of additional norepinephrine. Norepinephrine-stimulated growth in medium containing Fe-55 complexed with transferrin or lactoferrin resulted in uptake of radioactivity by bacterial cells. Moreover, norepinephrine-stimulated growth in medium containing [H-3] norepinephrine indicated concomitant uptake of norepinephrine. In each case, addition of excess iron did not affect growth but significantly reduced levels of radioactivity (Fe-55 or H-3) associated with bacterial cells. A role for catecholamine-mediated iron supply in the pathophysicology of infectious diseases is proposed.