Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet

Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet
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DOI:
10.1002/jcb.20481
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发表时间:
2005-08
影响因子:
4
通讯作者:
Yukako Yoshikumi;H. Mashima;N. Ueda;H. Ohno;J. Suzuki;Shigeyasu Tanaka;M. Hayashi;N. Sekine;H. Ohnishi;H. Yasuda;T. Iiri;M. Omata;T. Fujita;I. Kojima
Yukako Yoshikumi;H. Mashima;N. Ueda;H. Ohno;J. Suzuki;Shigeyasu Tanaka;M. Hayashi;N. Sekine;H. Ohnishi;H. Yasuda;T. Iiri;M. Omata;T. Fujita;I. Kojima
中科院分区:
生物学2区
文献类型:
--
作者:
Yukako Yoshikumi;H. Mashima;N. Ueda;H. Ohno;J. Suzuki;Shigeyasu Tanaka;M. Hayashi;N. Sekine;H. Ohnishi;H. Yasuda;T. Iiri;M. Omata;T. Fujita;I. Kojima

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胰腺AR42J细胞具有肠道内胚层前体细胞的多能性。β细胞素(BTC)和激活素A (Act)将它们转化为胰岛素分泌细胞。利用mRNA差异显示技术,我们发现了一种新的线粒体转运蛋白,该转运蛋白在分化过程中高度表达,并将其命名为柠檬酸转运蛋白样蛋白(CTPL)。最近研究表明,铁柔素1 (Sfxn1)是屈尾(f/f)小鼠的易感基因,而CTPL是铁柔素家族成员Sfxn3的大鼠同源蛋白。CTPL/Sfxn3像Sfxn1一样靶向线粒体膜。在胰岛素分泌细胞分化早期,CTPL/Sfxn3、Sfxn2和Sfxn5的表达水平上调,而Sfxn1和Sfxn3的表达水平没有变化。Sfxn家族成员均在大鼠胰岛中表达。与正常大鼠相比,链脲佐菌素诱导的糖尿病大鼠胰岛中CTPL/Sfxn3、Sfxn2和Sfxn5的表达水平也上调。在具有反义寡核苷酸的大鼠胰岛素瘤细胞系INS - 1中,CTPL/Sfxn3的下调不影响胰岛素分泌。综上所述,CTPL/Sfxn3和其他一些家族成员可能在胰腺β细胞的分化中作为通道或载体分子发挥重要作用,并与胰腺内分泌细胞的再生有关。©2005 Wiley‐Liss, Inc。
Pancreatic AR42J cells have the feature of pluripotency of the precursor cells of the gut endoderm. Betacellulin (BTC) and activin A (Act) convert them into insulin‐secreting cells. Using mRNA differential display techniques, we have identified a novel mitochondrial transporter, which is highly expressed during the course of differentiation, and have designated it citrate transporter protein‐like protein (CTPL). Recently sideroflexin 1 (Sfxn1) was shown to be a susceptible gene of flexed‐tail (f/f) mice, and CTPL has turned out to be a rat orthologous protein of Sfxn3, a member of sideroflexin family. CTPL/Sfxn3 was targeted to mitochondrial membrane like Sfxn1. The expression levels of CTPL/Sfxn3, Sfxn2, and Sfxn5 were upregulated in the early phase of differentiation into insulin‐secreting cells but the expression levels of Sfxn1 and Sfxn3 did not change. All Sfxn family members were expressed in rat pancreatic islet. The expression levels of CTPL/Sfxn3, Sfxn2, and Sfxn5 were also upregulated in islets of streptozotocin‐induced diabetic rats compared to normal rats. The downregulation of CTPL/Sfxn3 in a rat insulinoma cell line, INS‐1, with the antisense oligonucleotide did not affect the insulin secretion. Taken together, CTPL/Sfxn3 and some other family members might be important in the differentiation of pancreatic β‐cells as a channel or a carrier molecule and be related to the regeneration of pancreatic endocrine cells. © 2005 Wiley‐Liss, Inc.