RRC ID 52533
Author Shobatake R, Takasawa K, Ota H, Itaya-Hironaka A, Yamauchi A, Sakuramoto-Tsuchida S, Uchiyama T, Makino M, Sugie K, Takasawa S, Ueno S.
Title Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells.
Journal Int J Biochem Cell Biol
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.
Volume 95
Pages 100-107
Published 2018-2
DOI 10.1016/j.biocel.2017.12.012
PII S1357-2725(17)30324-2
PMID 29275211
MeSH Arcuate Nucleus of Hypothalamus / metabolism Arcuate Nucleus of Hypothalamus / pathology Binding Sites Cell Hypoxia Cell Line, Tumor Cell Survival GATA2 Transcription Factor / antagonists & inhibitors GATA2 Transcription Factor / chemistry GATA2 Transcription Factor / genetics GATA2 Transcription Factor / metabolism* GATA3 Transcription Factor / antagonists & inhibitors GATA3 Transcription Factor / chemistry GATA3 Transcription Factor / genetics GATA3 Transcription Factor / metabolism* Gene Deletion Gene Expression Regulation* Genes, Reporter Humans Nerve Tissue Proteins / antagonists & inhibitors Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Neurons / metabolism* Neurons / pathology Pro-Opiomelanocortin / chemistry Pro-Opiomelanocortin / genetics Pro-Opiomelanocortin / metabolism* Promoter Regions, Genetic RNA, Messenger / metabolism* Sleep Apnea Syndromes / metabolism Sleep Apnea Syndromes / pathology Time Factors Up-Regulation
IF 3.144
Times Cited 9
Human and Animal Cells SK-N-SH(RCB0426)