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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3454

Title: Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells.
Other Titles: 間欺的低酸素はヒト神経細胞においてGATA転写因子を介してPOMCとCARTのmRNAを増加させる
Authors: Shobatake, Ryogo
Takasawa, Ken
Ota, Hiroyo
Itaya-Hironaka, Asako
Yamauchi, Akiyo
Sakuramoto-Tsuchida, Sumiyo
Uchiyama, Tomoko
Makino, Mai
Sugie, Kazuma
Takasawa, Shin
Ueno, Satoshi
Keywords: Sleep apnea syndrome
Intermittent hypoxia
POMC (proopiomelanocortin)
CART (cocaine- and amphetamine-regulated transcript)
Issue Date: Feb-2018
Publisher: Elsevier
Citation: The international journal of biochemistry and cell biology Vol.95 p.100-107 (2018 Feb)
Abstract: Sleep apnea syndrome (SAS) is characterized by intermittent hypoxia (IH) during sleep. SAS and obesity are strongly related to each other. Here, we investigated the effect of IH on the expression of major appetite regulatory genes in human neuronal cells. We exposed NB-1, SH-SY5Y, and SK-N-SH human neuronal cells to IH (64 cycles of 5 min hypoxia and 10 min normoxia), normoxia, or sustained hypoxia for 24 h and measured the mRNA levels of proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), galanin, galanin-like peptide, ghrelin, pyroglutamylated RFamide peptide, agouti-related peptide, neuropeptide Y, and melanocortin 4 receptor by real-time RT-PCR. IH significantly increased the mRNA levels of POMC and CART in all the neuronal cells. Deletion analysis revealed that the -705 to -686 promoter region of POMC and the -950 to -929 region of CART were essential for the IH-induced promoter activity. As possible GATA factor binding sequences were found in the two regions, we performed real-time RT-PCR to determine which GATA family members were expressed and found that GATA2 and GATA3 mRNAs were predominantly expressed. Therefore, we introduced siRNAs against GATA2 and GATA3 into NB-1 cells and found that GATA2 and GATA3 siRNAs abolished the IH-induced up-regulation of both POMC and CART mRNAs. These results indicate that IH stress up-regulates the mRNA levels of anorexigenic peptides, POMC and CART, in human neuronal cells via GATA2 and GATA3. IH can have an anorexigenic effect on SAS patients through the transcriptional activation of POMC and CART in the central nervous system.
Description: 博士(医学)・甲第685号・平成30年6月27日
© 2017 Elsevier Ltd. All rights reserved.
URI: http://hdl.handle.net/10564/3454
ISSN: 13572725
Academic Degrees and number: 24601A685
Degree-granting date: 2018-06-27
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2018年度

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