Abstract
BackgroundSuccinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma. In the present study we investigated components of the oxidative phosphorylation system in human neuroblastoma tissue samples.MethodsSpectrophotometric measurements, immunohistochemical analysis and Western blot analysis were used to characterize the aerobic mitochondrial energy metabolism in neuroblastomas (NB).ResultsCompared to mitochondrial citrate synthase, SDH activity was severely reduced in NB (n = 14) versus kidney tissue. However no pathogenic mutations could be identified in any of the four subunits of SDH. Furthermore, no genetic alterations could be identified in the two novel SDH assembly factors SDHAF1 and SDH5. Alterations in genes encoding nfs-1, frataxin and isd-11 that could lead to a diminished SDH activity have not been detected in NB.ConclusionBecause downregulation of other complexes of the oxidative phosphorylation system was also observed, a more generalized reduction of mitochondrial respiration seems to be present in neuroblastoma in contrast to the single enzyme defect found in hereditary pheochromocytomas.
Highlights
Succinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma
Pheochromocytomas and paragangliomas frequently exhibit mutations in the succinate dehydrogenase (SDH) subunits SDHB, SDHC, SDHD indicating that these SDH subunits act as tumor suppressors in neuroendocrine tissues [2]
The aim of the present study was to determine if there are specific alterations of aerobic energy metabolism in NBs, especially of SDH, or if there is an overall downregulation of oxidative phosphorylation (OXPHOS) complexes
Summary
Succinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma. In the present study we investigated components of the oxidative phosphorylation system in human neuroblastoma tissue samples. According to the International Neuroblastoma (NB) Pathology Classification, NBs are defined as embryonal tumors of the sympathetic nervous system, derive from the neural crest and arise in the adrenal medulla, paravertebral sympathetic ganglia, and sympathetic paraganglia [1]. Paraganglioma and pheochromocytoma are histologically related to NB as they are all neural crest derived. Pheochromocytomas and paragangliomas frequently exhibit mutations in the succinate dehydrogenase (SDH) subunits SDHB, SDHC, SDHD indicating that these SDH subunits act as tumor suppressors in neuroendocrine tissues [2]. The SDH complex is composed of four subunits and contains a flavin molecule (FAD), non-heme iron centers and a b-type cytochrome as prosthetic groups. The complex is anchored by a large SDHC and a small
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