Silencing of the mitochondrial NADH shuttle component aspartate-glutamate carrier AGC1/Aralar1 in INS-1E cells and rat islets
Silencing of the mitochondrial NADH shuttle component aspartate-glutamate carrier AGC1/Aralar1 in INS-1E cells and rat islets
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DOI：
10.1042/bj20090729
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发表时间：
2009-12-15
影响因子：
4.1
通讯作者：
Maechler, Pierre
中科院分区：
文献类型：
--
作者：
Casimir, Marina;Rubi, Blanca;Maechler, Pierre
胞质区室和线粒体基质之间还原当量的转移是由 NADH 穿梭介导的。其中，苹果酸-天冬氨酸穿梭被认为在β细胞中发挥主要作用，以控制葡萄糖刺激的胰岛素分泌。 AGC1 或 Aralar1（天冬氨酸-谷氨酸载体 1）是苹果酸-天冬氨酸穿梭的关键组成部分。 AGC1 的过度表达增加了苹果酸-天冬氨酸穿梭的能力，从而增强了 INS-1E 细胞和大鼠胰岛中的代谢-分泌耦合。在本研究中，使用腺病毒介导的 shRNA（小发夹 RNA）递送，在相同的 β 细胞模型中实现了 AGC1 的敲低。与对照 INS-1E 细胞相比，AGC1 的下调减弱了 NADH 的形成（-57%；P
Transfer of reducing equivalents between cytosolic compartments and the mitochondrial matrix is mediated by NADH shuttles. Among these, the malate-aspartate shuttle has been proposed to play a major role in beta-cells for the control of glucose-stimulated insulin secretion. AGC1 or Aralar1 (aspartate-glutamate carrier 1) is a key component of the malate-aspartate shuttle. Overexpression of AGC1 increases the capacity of the malate-aspartate shuttle, resulting in enhanced metabolism-secretion coupling, both in INS-1E cells and rat islets. In the present study, knockdown of AGC1 was achieved in the same beta-cell models, using adenovirus-mediated delivery of shRNA (small-hairpin RNA). Compared with control INS-1E cells, down-regulation of AGC1 blunted NADH formation (-57%; P