A Fluorescent Benzo[g]isoquinoline-Based HIF Prolyl Hydroxylase Inhibitor for Cellular Imaging.
Marleen MayerKerstin FeyEva HeinzeChristian R WickMartine I AbboudTzu-Lan YehAnthony TumberNicole OrthGunnar SchleyBjörn BuchholzTimothy ClarkChristopher J SchofieldCarsten WillamNicolai BurzlaffPublished in: ChemMedChem (2018)
Prolyl hydroxylation domain (PHD) enzymes catalyze the hydroxylation of the transcription factor hypoxia-inducible factor (HIF) and serve as cellular oxygen sensors. HIF and the PHD enzymes regulate numerous potentially tissue-protective target genes which can adapt cells to metabolic and ischemic stress. We describe a fluorescent PHD inhibitor (1-chloro-4-hydroxybenzo[g]isoquinoline-3-carbonyl)glycine which is suited to fluorescence-based detection assays and for monitoring PHD inhibitors in biological systems. In cell-based assays, application of the fluorescent PHD inhibitor allowed co-localization with a cellular PHD enzyme and led to live cell imaging of processes involved in cellular oxygen sensing.
Keyphrases
- quantum dots
- transcription factor
- label free
- high resolution
- living cells
- endothelial cells
- induced apoptosis
- high throughput
- single cell
- stem cells
- genome wide
- cell therapy
- cell cycle arrest
- oxidative stress
- mesenchymal stem cells
- cell death
- cell proliferation
- signaling pathway
- dna methylation
- brain injury
- endoplasmic reticulum stress
- bone marrow
- fluorescent probe
- dna binding