Figure 4. MAOA expression increases ROS and the expression of HIF1α and HIF1α pathway genes.

(A) Deamination reaction catalyzed by monoamine oxidase (MAO) enzymes produces H₂0₂ as a reactive oxygen species (ROS) byproduct. (B) ROS levels are increased in PC3 cells expressing MAOA (*p<0.05). (C) Expression of MAOA in PC3 cells results in elevated nuclear HIF1α and NFκB protein. (D) Expression of MAOA in PC3 cells results in increased levels of transcripts encoding known HIF1A target genes. (E) Association of MAOA and HIF1 transcript level changes following chemotherapy. Plotted are the Log2 post-chemotherapy versus pre-chemotherapy transcript abundance ratios for each of 31 patients. The Pearson correlation value is 0.42 (p = 0.02). (F) Treatment of VCaP cells with the MAOA inhibitor clorgyline suppresses HIF1A expression. A four-fold reduction of HIF1A mRNA was quantitated by qRT-PCR at 48 hours relative to vehicle control (p<0.01).