Koehler-Stec E M, Simpson I A, Vannucci S J, Landschulz K T, Landschulz W H
Experimental Diabetes, Metabolism and Nutrition Section, Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Am J Physiol. 1998 Sep;275(3):E516-24. doi: 10.1152/ajpendo.1998.275.3.E516.
Although glucose is the major metabolic fuel needed for normal brain function, monocarboxylic acids, i.e., lactate, pyruvate, and ketone bodies, can also be utilized by the brain as alternative energy substrates. In most mammalian cells, these substrates are transported either into or out of the cell by a family of monocarboxylate transporters (MCTs), first cloned and sequenced in the hamster. We have recently cloned two MCT isoforms (MCT1 and MCT2) from a mouse kidney cDNA library. Northern blot analysis revealed that MCT1 mRNA is ubiquitous and can be detected in most tissues at a relatively constant level. MCT2 expression is more limited, with high levels of expression confined to testes, kidney, stomach, and liver and lower levels in lung, brain, and epididymal fat. Both MCT1 mRNA and MCT2 mRNA are detected in mouse brain using antisense riboprobes and in situ hybridization. MCT1 mRNA is found throughout the cortex, with higher levels of hybridization in hippocampus and cerebellum. MCT2 mRNA was detected in the same areas, but the pattern of expression was more specific. In addition, MCT1 mRNA, but not MCT2, is localized to the choroid plexus, ependyma, microvessels, and white matter structures such as the corpus callosum. These results suggest a differential expression of the two MCTs at the cellular level.
尽管葡萄糖是正常脑功能所需的主要代谢燃料,但单羧酸,即乳酸、丙酮酸和酮体,也可被大脑用作替代能量底物。在大多数哺乳动物细胞中,这些底物通过单羧酸转运体(MCTs)家族转运进出细胞,该家族最早在仓鼠中被克隆和测序。我们最近从小鼠肾脏cDNA文库中克隆了两种MCT亚型(MCT1和MCT2)。Northern印迹分析显示,MCT1 mRNA普遍存在,可在大多数组织中以相对恒定的水平检测到。MCT2的表达更有限,高水平表达局限于睾丸、肾脏、胃和肝脏,而在肺、脑和附睾脂肪中的表达水平较低。使用反义核糖探针和原位杂交在小鼠脑中检测到了MCT1 mRNA和MCT2 mRNA。MCT1 mRNA在整个皮质中都有发现,在海马体和小脑中杂交水平更高。在相同区域检测到了MCT2 mRNA,但表达模式更具特异性。此外,MCT1 mRNA定位于脉络丛、室管膜、微血管和白质结构如胼胝体,而MCT2则没有。这些结果表明这两种MCT在细胞水平上存在差异表达。