Ngwaahịa

Ihe karịrị 70% nke gliomas dị ala na-ebu mmụgharị heterozygous R132H na mkpụrụ ndụ mkpụrụ ndụ maka isocitrate dehydrogenase 1 (IDH1).Nke a na-enye enzyme na ikike ọhụrụ iji gbanwee α-ketoglutarate na 2-hydroxyglutarate, n'ikpeazụ na-eduga na tumorigenesis.Isi mmalite nke mmepụta 2-hydroxyglutarate bụ glutamine, nke, na ọrịa kansa, bụkwa isi iyi nke tricarboxylic acid cycle (TCA) anaplerosis.Isi mmalite nke anaplerosis bụ pyruvate flux site na pyruvate carboxylase (PC), nke bụ ụzọ a na-ahụkarị na astrocytes nkịtị.Ebumnuche nke ọmụmụ a bụ iji chọpụta ma PC na-eje ozi dị ka isi iyi nke TCA anaplerosis na IDH1 mutant sel ebe a na-eji glutamine eme ihe maka mmepụta 2-hydroxyglutarate.Flux nke pyruvate site na PC na site na pyruvate dehydrogenase (PDH) ka ekpebisiri ike site na iji magnetik resonance spectroscopy iji nyochaa akara nke [2-¹³C] glucose enwetara ¹³ C-labe led glutamate na glutamine.A na-eji nyocha ọrụ, RT-PCR na ihichapụ ọdịda anyanwụ wee nyochaa okwu na ọrụ nke enzymes dị mkpa.A na-enyocha data Cancer Genome Atlas (TCGA) iji nyochaa okwu nke enzymes na sample glioma mmadụ. E jiri ya tụnyere ụdị anụ ọhịa, mkpụrụ ndụ IDH1 mutant na-abawanye ụbara site na PC.Ejikọtara nke a na mmụba dị ukwuu na ọrụ PC na nkwupụta.N'otu oge ahụ, ọrụ PDH na-ebelata nke ukwuu, ma eleghị anya na-agbaziri ya site na mmụba nke ukwuu inhibitory PDH phosphorylation site PDH kinase 3. N'ikwekọ na nlele na sel, nyocha nke data TCGA gosiri mmụba dị ukwuu na okwu PC na IDH mutant-na-egosipụta ụdị glioma mmadụ ma e jiri ya tụnyere ọhịa- ụdị IDH.Nchọpụta anyị na-atụ aro na mgbanwe na PC na PDH nwere ike ịbụ akụkụ dị mkpa nke ngbanwe nke cell na mutation IDH1 ma nwee ike bụrụ ebumnuche ọgwụgwọ.