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Glucose metabolism in human gliomas: Correspondence ofin situ andin vitro metabolic rates and altered energy metabolism
Authors:Juan Galarraga  David J. Loreck  Jon F. Graham  Robert L. DeLaPaz  B. H. Smith  Douglas Hallgren  C. J. Cummins
Affiliation:(1) Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institute of Health, 20205 Bethesda, Maryland;(2) Division of Neurosurgery, Walter Reed Army Medical Center, 20307 Washington, D.C.;(3) Division of Neurosurgery, Department of Radiology, Massachusetts General Hospital, 02114 Boston, Massachusetts;(4) Division of Neurosurgery, Memorial Sloan-Kettering Cancer Center, 10021 New York, New York;(5) Department of Medicine, Sinia Hospital, Belvedere Avenue at Green Spring, 21215 Baltimore, Maryland
Abstract:The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by ftuorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I–III gliomas had a glucose consumption rate of 2–3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measuredin situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the gliomaderived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomasin situ and (2) are significantly altered in several aspects of their glycolytic metabolism.
Keywords:energy metabolism  glia  gliomas  positron emission computed tomography
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