ABSTRACT
The original version of this article unfortunately contained an error in author group. The authors Yi-Xiang See, Xin Chen, Zi-Kai Chen and Ze-Bin Huang were inadvertently included in the article.
ABSTRACT
Glucose and glutamine are two essential ingredients for cell growth. Glycolysis and glutaminolysis can be linked by glutamine: fructose-6-phosphate aminotransferase (GFAT, composed of GFAT1 and GFAT2) that catalyzes the synthesis of glucosamine-6-phosphate and glutamate by using fructose-6-phosphate and glutamine as substrates. The role of mammalian target of rapamycin (MTOR, composed of MTOR1 and MTOR2) in regulating glycolysis has been explored in human cancer cells. However, whether MTOR can interact with GFAT to regulate glucosamine-6-phosphate is poorly understood. In this study, we report that GFAT1 is essential to maintain the malignant features of GBM cells. And MTOR2 rather than MTOR1 plays a robust role in promoting GFAT1 protein activity, and accelerating the progression of glucosamine-6-phosphate synthesis, which is not controlled by the PI3K/AKT signaling. Intriguingly, high level of glucose or glutamine supply promotes MTOR2 protein activity. In turn, up-regulating glycolytic and glutaminolytic metabolisms block MTOR dimerization, enhancing the release of MTOR2 from the MTOR complex. As a transcriptional factor, C-MYC, directly targeted by MTOR2, promotes the relative mRNA expression level of GFAT1. Notably, our data reveal that GFAT1 immunoreactivity is positively correlated with the malignant grades of glioma patients. Kaplan-Meier assay reveals the correlations between patients' 5-year survival and high GFAT1 protein expression. Taken together, we propose that the MTOR2/C-MYC/GFAT1 axis is responsible for the modulation on the crosstalk between glycolysis and glutaminolysis in GBM cells. Under the condition of accelerated glycolytic and/or glutaminolytic metabolisms, the MTOR2/C-MYC/GFAT1 axis will be up-regulated in GBM cells.
Subject(s)
Glioblastoma/metabolism , Glucosamine/analogs & derivatives , Glucose-6-Phosphate/analogs & derivatives , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism , Glutamine/metabolism , Proto-Oncogene Proteins c-myc/metabolism , TOR Serine-Threonine Kinases/metabolism , Animals , Antigens, Neoplasm/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Glucosamine/biosynthesis , Glucose/metabolism , Glucose-6-Phosphate/biosynthesis , Humans , Male , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Phosphatidylinositol 3-Kinases/metabolism , Protein Multimerization , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
OBJECTIVE: To further reveal the chemical constituents of Polypodium hastatum, volatile components from this plant were investigated. METHODS: The volatile components were extracted under reflux from the whole plant of Polypodium hastatum, and then analyzed qualitatively and quantitatively by GC-MS. RESULTS: 60 volatile components were detected and of all components detected, the structures and relative contents of 34 volatile compounds were elucidated. CONCLUSION: In the volatile components identified, most are fatty acid esters, especially methyl and ethyl esters, which compose the major volatile chemical constituents of Polypodium hastatum.
Subject(s)
Oils, Volatile/chemistry , Plant Oils/chemistry , Polypodium/chemistry , Fatty Acids , Gas Chromatography-Mass SpectrometryABSTRACT
OBJECTIVE: To investigate the chemical constituents of Kalopanax septemlobus. METHODS: Chromatographic techniques including silica gel, gel, semi-preparative HPLC and PTLC as well as recrystallization were employed in the isolation and purification, and the structures were elucidated by spectral analysis and physical and chemical properties. RESULTS: 6 compounds were identified as liriodendrin (1), (-) -syringarenol (2), trans-coniferyl aldehyde (3), trans-caffeic acid (4), beta-daucosterol (5), beta-sitosterol (6). CONCLUSION: Compounds 2 -5 are obtained from this genus for the first time.
Subject(s)
Aldehydes/isolation & purification , Furans/isolation & purification , Kalopanax/chemistry , Lignans/isolation & purification , Plant Roots/chemistry , Acrolein/analogs & derivatives , Aldehydes/chemistry , Caffeic Acids/chemistry , Caffeic Acids/isolation & purification , Furans/chemistry , Lignans/chemistry , Molecular Structure , Plant Bark/chemistry , Plants, Medicinal/chemistry , Sitosterols/chemistry , Sitosterols/isolation & purificationABSTRACT
OBJECTIVE: To study the chemical constituents of Wikstroemia indica. METHODS: The constituents were isolated and purified by silica gel chromatography repeatedly, and the structures were determined by spectral data and chemical envidance. RESULTS: Six compounds were isolated from its petroleum ether, dichloromethane, acetone and methanol extracts and identified as: daphnoretin-7-O-beta-D-glucoside (1), aloe-emodin (2), kaempferol (3), 29-nonacosanolide (4), 1-octadecanol (5), beta-sitosterol (6). CONCLUSION: Compounds 2, 4, 5 are isolated from this plant for the first time.
