Copper Deficiency and Mitochondrial Biogenesis: The role of transcriptional factors PPAR‐alpha, PGC‐1 alpha and NFkb1

Abstract

Purpose We hypothesized that increased mitochondrial proliferation demonstrated in hearts from copper deficient rats is due to an increase of the transcriptional factor PGC-1 alpha, which regulates transcriptional activity for many of the genes that encode for mitochondrial proteins. Methods Long-Evan rats were placed on either a copper-deficient or copper adequate diet 3 days post-weaning. At 5 weeks rats were sacrificed, blood was collected from the left ventricular cavity, as well as collection of the heart and liver tissue, which were preserved for further analysis. Copper deficiency status was assessed using previously established assays. Custom arrays were hybridized with cRNA probes synthesized from collected heart tissue. Hybridized arrays were detected with CDP-star, a chemiluminescent tag, and images were captured with Alpha-Innotech-CCD camera. Array images were analyzed with Superarray software GEArray Suite. Results Our results did not demonstrate any significant increase in PGC-1 alpha or PPAR-alpha as we had predicted. Consistent with previous data, an up-regulation of genes that encode for collagen type 3, fibronectin, and elastin were found. Interestingly, there was a significant increase in NFkb1. NFkb is a transcriptional factor that has been implicated in numerous pathways that regulate cellular growth and proliferation. Future studies should take note of these findings. Supported by funds from K-State Research and Extension, Multi-State Project W-1002.