Pyatskowit Joshua W, Prohaska Joseph R
Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2007 Mar;145(2):275-81. doi: 10.1016/j.cbpc.2006.12.013. Epub 2007 Jan 12.
Limiting dopamine beta-monooxygenase results in lower norepinephrine (NE) and higher dopamine (DA) concentrations in copper-deficient Cu- tissues compared to copper-adequate Cu+ tissues. Mice and rat offspring were compared to determine the effect of differences in dietary copper Cu deficiency started during gestation or lactation on catecholamine, NE and DA, content in brain and heart. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu- diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 12 and 27. For both rat and mouse Cu- tissue, NE and DA changes were greater at later ages. Though Cu restriction began earlier in rats than mice in the gestational model, brain NE reduction was more severe in Cu- mice than Cu- rats. Cardiac NE reduction was similar in Cu- rodents in the gestation models. In the lactation model, mouse catecholamines were altered more than rat catecholamines. Furthermore, following lactational Cu deficiency Cu- mice were anemic and exhibited cardiac hypertrophy, Cu- rats displayed neither phenotype. Within a species, changes were more severe and proportional to the length of Cu deprivation. Lactational Cu deficiency in mice had greater consequences than in rats.
与铜充足的Cu+组织相比,限制多巴胺β-单加氧酶会导致缺铜的Cu-组织中去甲肾上腺素(NE)浓度降低,多巴胺(DA)浓度升高。对小鼠和大鼠后代进行比较,以确定妊娠或哺乳期开始的饮食铜差异(铜缺乏)对脑和心脏中儿茶酚胺、NE和DA含量的影响。给霍尔茨曼大鼠和远交群白化病Hsd:ICR(CD-1)小鼠的母鼠喂食低铜饮食,并饮用去离子水或补充铜的水。在出生后12至27天的时间点对后代进行采样。对于大鼠和小鼠的Cu-组织,NE和DA的变化在较晚年龄时更大。尽管在妊娠模型中大鼠比小鼠更早开始限制铜摄入,但缺铜小鼠脑中NE的减少比缺铜大鼠更严重。在妊娠模型中,缺铜啮齿动物心脏中NE的减少情况相似。在哺乳模型中,小鼠儿茶酚胺的改变比大鼠儿茶酚胺的改变更大。此外,哺乳期缺铜后,缺铜小鼠出现贫血并表现出心脏肥大,缺铜大鼠则未表现出这两种表型。在同一物种内,变化更严重,且与铜缺乏的持续时间成正比。小鼠哺乳期缺铜的后果比大鼠更严重。