| First Author | Arreola A | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e98705 |
| PubMed ID | 24879016 | Mgi Jnum | J:374559 |
| Mgi Id | MGI:6243720 | Doi | 10.1371/journal.pone.0098705 |
| Citation | Arreola A, et al. (2014) HIF1alpha and HIF2alpha exert distinct nutrient preferences in renal cells. PLoS One 9(5):e98705 |
| abstractText | BACKGROUND: Hypoxia Inducible Factors (HIF1alpha and HIF2alpha) are commonly stabilized and play key roles related to cell growth and metabolic programming in clear cell renal cell carcinoma. The relationship of these factors to discretely alter cell metabolic activities has largely been described in cancer cells, or in hypoxic conditions, where other confounding factors undoubtedly compete. These transcription factors and their specific roles in promoting cancer metabolic phenotypes from the earliest stages are poorly understood in pre-malignant cells. METHODS: We undertook an analysis of SV40-transformed primary kidney epithelial cells derived from newborn mice genetically engineered to express a stabilized HIF1alpha or HIF2alpha transgene. We examined the metabolic profile in relation to each gene. RESULTS: Although the cells proliferated similarly, the metabolic profile of each genotype of cell was markedly different and correlated with altered gene expression of factors influencing components of metabolic signaling. HIF1alpha promoted high levels of glycolysis as well as increased oxidative phosphorylation in complete media, but oxidative phosphorylation was suppressed when supplied with single carbon source media. HIF2alpha, in contrast, supported oxidative phosphorylation in complete media or single glucose carbon source, but these cells were not responsive to glutamine nutrient sources. This finding correlates to HIF2alpha-specific induction of Glul, effectively reducing glutamine utilization by limiting the glutamate pool, and knockdown of Glul allows these cells to perform oxidative phosphorylation in glutamine media. CONCLUSION: HIF1alpha and HIF2alpha support highly divergent patterns of kidney epithelial cell metabolic phenotype. Expression of these factors ultimately alters the nutrient resource utilization and energy generation strategy in the setting of complete or limiting nutrients. |
