title: Hypoxia-inducible factor-1α upregulates tyrosine hydroxylase and dopamine transporter by nuclear receptor ERRγ in SH-SY5Y cells.
abstract: Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor relevant to the development of many mammalian organs including the brain. However, the molecular mechanisms by which signaling events mediate neuronal differentiation have not been fully elucidated. In the present study, we show for the first time that the orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated by HIF-1α and plays essential roles in HIF-1α-induced upregulation of dopaminergic marker molecules such as tyrosine hydroxylase and dopamine transporter. We found that deferoxamine upregulated HIF-1α and enhanced the dopaminergic phenotype and neurite outgrowth of SH-SY5Y cells. Deferoxamine activated transcription and protein expression of ERRγ, and deferoxamine-induced upregulation of tyrosine hydroxylase and dopamine transporter was attenuated by using the ERRγ inverse agonist or silencing ERRγ. Altogether, these results suggest that HIF-1α can positively regulate the dopaminergic phenotype through ERRγ. This study could provide new perspectives for understanding the mechanisms underlying the promotion of dopaminergic neuronal differentiation by hypoxia.
authors: aCollege of Pharmacy, CHA University, Seongnam bInAm Neuroscience Research Center, Wonkwang University, Sanbon Hospital, Gunpo cSchool of Biological Sciences and Technology, National Creative Research Initiatives Center for Nuclear Receptor Signals and Hormone Research Center, Chonnam National University, Gwangju dCollege of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
authors: Juhee
authors: J
authors: Lim
authors: Hyo-In
authors: HI
authors: Kim
authors: Yeojin
authors: Y
authors: Bang
authors: Wongi
authors: W
authors: Seol
authors: Hueng-Sik
authors: HS
authors: Choi
authors: Hyun Jin
authors: HJ
authors: Choi
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C490917:ESRRG protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011960:Receptors, Estrogen; D014446:Tyrosine 3-Monooxygenase