Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells. (February 2018)

• Record Type: Journal Article
• 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
• Is Part Of: International journal of biochemistry & cell biology. Volume 95(2018)
• Page Start: 100
• Page End: 107
• Publication Date: 2018-02
• Subjects: AGRP agouti-related peptide -- ARC hypothalamic arcuate nucleus -- BMI body mass index -- CART cocaine- and amphetamine-regulated transcript -- CNS central nervous system -- FCS fetal calf serum -- GAL galanin -- GALP galanin-like peptide -- GATA GATA-binding factor -- GHRL ghrelin -- IH intermittent hypoxia -- MC4R melanocortin 4 receptor -- NPY neuropeptide Y -- OSA obstructive sleep apnea -- POMC proopiomelanocortin -- QRFP pyroglutamylated RFamide peptide -- RT-PCR reverse transcription-polymerase chain reaction -- ROS reactive oxygen species -- SAS sleep apnea syndrome -- SH sustained hypoxia -- siRNA small interfering RNA; Sleep apnea syndrome -- Intermittent hypoxia -- Appetite -- POMC (proopiomelanocortin) -- CART (cocaine- and amphetamine-regulated transcript) -- GATA; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2017.12.012
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: IH up-regulates POMC and CART mRNAs in human neuronal cells. Transcriptional activation of POMC and CART by IH requires both GATA-2 and GATA-3. IH may show anorexigenic effects on SAS patients. 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.