Nose Yasuhiro, Kim Byung-Eun, Thiele Dennis J
Department of Pharmacology and Cancer Biology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cell Metab. 2006 Sep;4(3):235-44. doi: 10.1016/j.cmet.2006.08.009.
The trace element copper (Cu) is a cofactor for biochemical functions ranging from energy generation to iron (Fe) acquisition, angiogenesis, and free radical detoxification. While Cu is essential for life, the molecules that mediate dietary Cu uptake have not been identified. Ctr1 is a homotrimeric protein, conserved from yeast to humans, that transports Cu across the plasma membrane with high affinity and specificity. Here we describe the generation of intestinal epithelial cell-specific Ctr1 knockout mice. These mice exhibit striking neonatal defects in Cu accumulation in peripheral tissues, hepatic Fe overload, cardiac hypertrophy, and severe growth and viability defects. Consistent with an intestinal Cu absorption block, the growth and viability defects can be partially rescued by a single postnatal Cu administration, indicative of a critical neonatal metabolic requirement for Cu that is provided by intestinal Ctr1. These studies identify Ctr1 as the major factor driving intestinal Cu absorption in mammals.
微量元素铜（Cu）是多种生化功能的辅助因子，这些功能涵盖从能量产生到铁（Fe）摄取、血管生成和自由基解毒等方面。虽然铜对生命至关重要，但介导膳食铜摄取的分子尚未被确定。铜转运蛋白1（Ctr1）是一种同源三聚体蛋白，从酵母到人类都保守存在，它以高亲和力和特异性将铜转运穿过质膜。在此，我们描述了肠道上皮细胞特异性Ctr1基因敲除小鼠的产生。这些小鼠在外周组织铜积累、肝脏铁过载、心脏肥大以及严重的生长和生存能力缺陷方面表现出明显的新生期缺陷。与肠道铜吸收受阻一致，生长和生存能力缺陷可通过出生后单次给予铜得到部分挽救，这表明肠道Ctr1提供的铜对新生期代谢至关重要。这些研究确定Ctr1是驱动哺乳动物肠道铜吸收的主要因素。
