We report a 1H and 13C HR-MAS NMR study of normal and diseased brain regions of rats bearing C6 gliomas implanted. The detection of selectively enriched metabolites through ex vivo HR-MAS spectroscopy and the correlations with the expression of the genes involved in the glycolytic metabolism are the aims of this work. C6 gliomas were induced in Wistar rats and tumour growth was evaluated in vivo using T1 and T2 weighted MRI. Three weeks after C6 implantation, rats were infused with [1-13C] glucose and then cerebral metabolism was arrested. The fixed brain was removed from the skull and five biopsies were taken from different brain regions (fig.1). The proton spectra show the increase in lactate and mobile lipids in the tumour biopsies and the 13C spectra present a significant increase of (3-13C) lactate and decrease of (4-13C) glutamate and (4-13C) glutamine, revealing a marked increase in glycolytic metabolism in the tumour. Then, we investigated the individual expression of specific genes coding for some enzymes involved in the glycolytic pathway, to improve our understanding of the genetic basis of the metabolic profile observed by 13C HR-MAS. For example, the study of the genes expression encoding for Lactate Dehydrogenase (LDH) enzyme shows the increased expression and the activity of the gene in region 3 and 4, in agreement with the HR-MAS spectra. The Lactate Dehydrogenase is an enzyme that catalyzes the conversion of lactate to pyruvate. This is an important step in energy production in cells. Increase of LDH indicates cellular death or leakage of the enzyme from the cell. Indeed, 13C HR-MAS reveals important metabolic changes in different regions of the brain of rats bearing C6 gliomas, previously not detectable by in vivo or in vitro 13C NMR. The glycolysis genes studied in this work improved our understanding of the metabolic profile observed by 13C HR-MAS spectroscopy in different brain regions of rats bearing C6 gliomas.
V. Righi, P. Lopez-Carruba, L. Schenetti, A. Mucci, V. Tugnoli, M.L. Garcia-Martin, et al. (2010). Detecting the transition from normal to malignant phenotype in the brain of rats bearing implanted C6 gliomas by multinuclear HR MAS and genomic analysis.. s.l : s.n.
Detecting the transition from normal to malignant phenotype in the brain of rats bearing implanted C6 gliomas by multinuclear HR MAS and genomic analysis.
RIGHI, VALERIA;TUGNOLI, VITALIANO;
2010
Abstract
We report a 1H and 13C HR-MAS NMR study of normal and diseased brain regions of rats bearing C6 gliomas implanted. The detection of selectively enriched metabolites through ex vivo HR-MAS spectroscopy and the correlations with the expression of the genes involved in the glycolytic metabolism are the aims of this work. C6 gliomas were induced in Wistar rats and tumour growth was evaluated in vivo using T1 and T2 weighted MRI. Three weeks after C6 implantation, rats were infused with [1-13C] glucose and then cerebral metabolism was arrested. The fixed brain was removed from the skull and five biopsies were taken from different brain regions (fig.1). The proton spectra show the increase in lactate and mobile lipids in the tumour biopsies and the 13C spectra present a significant increase of (3-13C) lactate and decrease of (4-13C) glutamate and (4-13C) glutamine, revealing a marked increase in glycolytic metabolism in the tumour. Then, we investigated the individual expression of specific genes coding for some enzymes involved in the glycolytic pathway, to improve our understanding of the genetic basis of the metabolic profile observed by 13C HR-MAS. For example, the study of the genes expression encoding for Lactate Dehydrogenase (LDH) enzyme shows the increased expression and the activity of the gene in region 3 and 4, in agreement with the HR-MAS spectra. The Lactate Dehydrogenase is an enzyme that catalyzes the conversion of lactate to pyruvate. This is an important step in energy production in cells. Increase of LDH indicates cellular death or leakage of the enzyme from the cell. Indeed, 13C HR-MAS reveals important metabolic changes in different regions of the brain of rats bearing C6 gliomas, previously not detectable by in vivo or in vitro 13C NMR. The glycolysis genes studied in this work improved our understanding of the metabolic profile observed by 13C HR-MAS spectroscopy in different brain regions of rats bearing C6 gliomas.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
