Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 P67 | DOI: 10.1530/endoabs.32.P67

ECE2013 Poster Presentations Adrenal Medulla (5 abstracts)

Succinate dehydrogenase subunit B mutations modify human neuroblastoma cell metabolism and proliferation

Benedetta Zampetti 1 , Elena Rapizzi 1, , Tonino Ercolino 2 , Rossella Fucci 1, , Roberta Felici 1 , Daniele Guasti 1 , Valentino Giachè 1 , Daniele Bani 1 , Alberto Chiarugi 1 & Massimo Mannelli 1,

1University of Florence, Florence, Italy; 2Azienda Ospedaliera Universitaria Careggi, Florence, Italy; 3Istituto Toscano Tumori, Florence, Italy.

Paragangliomas (PGLs) are rare neuroendocrine tumors. About 30–40% of these tumors are mutated in different susceptibility genes, including those encoding the different subunits of the succinate dehydrogenase, a complex involved both in the tricarboxylic acid cycle and in the oxygen transport chain. The aim of this project was to investigate whether SDHB mutations may account for alterations in cell metabolism and functions. Since PGL cell lines are not available, we used the neuroblastoma cell line (SK-N-AS) stably transfected with the wild-type human SDHB, or different SDHB mutated constructs carrying the most significant mutations found in our patients affected by PGLs.

Interestingly, we found that all the SDHB mutated cell clones showed a specific reduction of the SDH enzyme activity. They also showed reduced oxygen consumption. Surprisingly and unexpectedly, in all the SDHB mutated clones we found a significant decrease in glucose uptake and in lactate concentration in the culture medium, while ATP production, was significantly higher, thus suggesting a shift in the utilization of the lactate metabolite towards glucose for energy production. Finally, we found that these metabolic changes are associated to increased potential in cell proliferation and migration. Overall, these data demonstrate that SDHB mutations deeply affect cellular metabolism and functions.

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