R132H-mutation of isocitrate dehydrogenase-1 is not sufficient for HIF-1α upregulation in adult glioma
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Mutations affecting codon 132 of the enzyme cytosolic isocitrate dehydrogenase 1 (IDH-1) have been found in 68–86% of World Health Organization (WHO) grade II and III astrocytic and oligodendroglial tumors in adults, as well as in the majority of WHO grade IV secondary glioblastomas that evolved from these lower-grade tumors [3, 4, 8]. IDH-1 is localized in the cytoplasm and peroxisomes and serves as a major source for cytosolic nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is necessary for the regeneration of reduced glutathione, which functions as the main antioxidant in mammalian cells. Glioma-specific mutations in IDH-1 usually affect the amino acid arginine at position 132 of the amino acid sequence [3, 5, 8], resulting in a substitution of histidine for arginine. This mutation only affects one allele and results in a decrease in IDH-1 activity. Inactivation of IDH-1 has been linked to elevated oxidative stress, which has been hypothesized to confer an increased...
KeywordsNicotinamide Adenine Dinucleotide Phosphate Oligodendroglial Tumor Secondary Glioblastoma Primary GBMs Mutant Glioma
This work was supported by grants to D.Z. from the National Institutes of Health (R01 CA100426 and R21 NS065280-01) and the Musella Foundation.