Peroxisomal proliferator activator receptor gamma coactivator (PGC)-1alpha induces both mitochondrial biogenesis and angiogenesis in skeletal muscle. Results: Hypoxic induction of an alternative spliced form of PGC-1alpha induces only angiogenesis in skeletal muscle, and not mitochondrial biogenesis. Conclusion: Alternative splicing of PGC-1alpha explains how PGC-1alpha achieves specific induction of angiogenesis during hypoxia. Significance: The findings suggest novel ways to induce

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... s in muscle without simultaneously inducing mitochondrial biogenesis. ABSTRACT The transcriptional coactivator peroxisome proliferator-activator receptor gamma coactivator (PGC)-1α is required for full hypoxic induction of vascular endothelial growth factor (VEGF) in skeletal muscle cells. Under normoxic conditions, PGC-1α also strongly induces mitochondrial biogenesis, but PGC-1α does not activate this program under hypoxic conditions. How this specificity is achieved is not known. We show here that hypoxia specifically induces NT-PGC-1α, a known alternatively spliced species encoding for a truncated form of PGC-1α. NT-PGC-1α strongly induces VEGF expression, while having little effect on mitochondrial genes. Conditioned medium from cells expressing NT-PGC-1α robustly induces endothelial migration http://www.jbc.org/cgi/