Abstract
The ubiquitous metabolic intermediary and nucleoside adenosine is a “master regulator” in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. ADK protein exists in the two isoforms nuclear ADK-L, and cytoplasmic ADK-S, which are subject to dynamic expression changes during brain development and in response to brain injury; however, gene expression changes of the Adk gene as well as regulatory mechanisms that direct the cell-type and isoform specific expression of ADK have never been investigated. Here we analyzed potential gene regulatory mechanisms that may influence Adk expression including DNA promoter methylation, histone modifications and transcription factor binding. Our data suggest binding of transcription factor SP1 to the Adk promoter influences the regulation of Adk expression.
Highlights
Adenosine kinase (ADK; EC 2.7.1.20) is an evolutionarily conserved phosphotransferase converting the purine ribonucleoside adenosine into 5′-adenosine-monophosphate (AMP) (Park and Gupta, 2008)
Our findings indicate that Adk gene expression is tightly controlled during early postnatal brain development both in a cell-type and isoform selective manner
Two selective time points were investigated, P4 and P14, respectively, flanking the narrow time window when Adk expression changes from the long neuronal to the short glial isoform
Summary
Adenosine kinase (ADK; EC 2.7.1.20) is an evolutionarily conserved phosphotransferase converting the purine ribonucleoside adenosine into 5′-adenosine-monophosphate (AMP) (Park and Gupta, 2008) This enzymatic reaction plays a fundamental role in determining the tissue tone of adenosine, which fulfills essential functions as a homeostatic and metabolic regulator in all living systems (Boison, 2013). Adenosine plays a key role in enzyme catalysis as part of the coenzymes nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD) (Denessiouk et al, 2001). It impacts intracellular signaling through four different types of adenosine receptors, which combine to regulate the second messenger cAMP (Fredholm et al, 2000). It is further an important regulator of epigenetic processes through its link to the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
