Peroxiredoxin, a mitochondrial‐specific peroxidase, as a possible key regulator of the β‐adrenergic receptor anti‐apoptotic pathway

We previously reported a β‐adrenergic receptor (βAR) modulation of apoptosis requiring formation of a β‐arrestin/heat shock protein (HSP) 27 signaling complex for protection against program cell death. Our hypothesis is that a protective mechanism for this signalosome occurs by localized cellular trafficking of specific proteins. Non‐biased gene microarray profiling was used in epithelial (UROtsa) cells to identify gene products altered after co‐incubation with isoproterenol (ISO) and an apoptotic inducer, staurosporine (STS). Gene products found significantly changed when compared to STS alone included PRX, a mitochondrial peroxidase, FBXO28, a nuclear ubiquitin ligase and ZNF638, a pro‐apoptotic transcription factor. Quantitative real‐time PCR was used to validate changes of these gene products. There was increased transcription significantly different from STS only for PRX and FBXO in cells treated with ISO plus STS. Similar results were found for PRX using a neuronal cell model. Conversely, there was a significant decrease in ZNF638 transcription for UROtsa cells treated with ISO plus STS when compared to STS alone. All results corroborate observations from the gene microarray analysis. Higher PRX expression seen with concurrent ISO incubation is hypothesized as a compensatory mechanism for the increased O 2 − production initiated by STS. Supported by a SURF from ASPET and NIH grant P20RR016741.