Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet.
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 beta-cells as a channel or a carrier molecule and be related to the regeneration of pancreatic endocrine cells.
Yoshikumi
Yukako
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Mashima
Hirosato
H
Ueda
Namiki
N
Ohno
Hideki
H
Suzuki
Junko
J
Tanaka
Shigeyasu
S
Hayashi
Michio
M
Sekine
Nobuo
N
Ohnishi
Hirohide
H
Yasuda
Hiroshi
H
Iiri
Taroh
T
Omata
Masao
M
Fujita
Toshiro
T
Kojima
Itaru
I
D000818:Animals; D027682:Cation Transport Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D027682:Cation Transport Proteins; D007328:Insulin; D012333:RNA, Messenger; C506522:Sfxn3 protein, mouse; C506521:Sfxn3 protein, rat