Molecular characterization of β2 adrenergic receptor haplotypes Public Deposited

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Alternate title
  • Molecular characterization of [beta]2 adrenergic receptor haplotypes
Last Modified
  • March 21, 2019
Creator
  • Higgins, Thomas John
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • Adrenergic receptor β2 (ADRB2) is a primary target for epinephrine. It is critical in mediating physiological responses to environmental stressors and affects a complex array of psychological and physiological characteristics: including asthma, hypertension, and pain sensitivity. We searched the ADRB2 promoter region for transcriptional activator putative binding sites, which revealed CREB, p65, and C/EBP binding sites. We constructed a luciferase reporter vector containing three major polymorphic variant haplotypes of a 2.0 kb human ADRB2 promoter region, and transiently transected the constructs into liver, neuronal, and immune cell lines. We demonstrated; a) different levels of basal promoter activity related to three major human haplotypes; b) tissue specific regulation of ADRB2 promoter at the basal level and upon treatment; c) haplotypes exhibited similar response patterns, demonstrating haplotype-independent transcription regulation by C/EBP, NFκB, and cAMP. These results are the first to demonstrate haplotype-dependent regulation of ADRB2 by cAMP, NFκB, and C/EBP pathways.
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  • In Copyright
Advisor
  • Diatchenko, Luda
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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