Kayayyaki

Fiye da kashi 70% na ƙananan gliomas suna ɗauke da maye gurbi na heterozygous R132H a cikin coding na gene don isocitrate dehydrogenase 1 (IDH1).Wannan yana ba da enzyme tare da sabon ikon canza α-ketoglutarate zuwa 2-hydroxyglutarate, a ƙarshe yana haifar da tumorigenesis.Babban tushen samar da 2-hydroxyglutarate shine glutamine, wanda, a cikin ciwon daji, kuma shine tushen tricarboxylic acid cycle (TCA) anaplerosis.Madadin tushen anaplerosis shine pyruvate flux ta hanyar pyruvate carboxylase (PC), wanda shine hanyar gama gari a cikin taurari na al'ada.Manufar wannan binciken shine don sanin ko PC yana aiki a matsayin tushen TCA anaplerosis a cikin kwayoyin mutant IDH1 inda ake amfani da glutamine don samar da 2-hydroxyglutarate.Flux na pyruvate ta PC kuma ta hanyar pyruvate dehydrogenase (PDH) an ƙaddara ta hanyar yin amfani da siginar maganadisu na maganadisu don bincika lakabin [2-¹³C] wanda aka samu ¹³ C-lakabin glutamate da glutamine.An yi amfani da ƙididdigar ayyuka, RT-PCR da ɓarkewar yamma don bincika magana da ayyukan enzymes masu dacewa.An yi nazarin bayanan Ciwon daji Genome Atlas (TCGA) don tantance maganganun enzymes a cikin samfuran glioma na ɗan adam. Idan aka kwatanta da nau'in nau'in daji, ƙwayoyin IDH1 na mutant sun ƙara haɓaka juzu'i ta hanyar PC.Wannan yana da alaƙa da haɓaka mai girma a cikin ayyukan PC da magana.A lokaci guda, ayyukan PDH ya ragu sosai, mai yiwuwa matsakanci ta hanyar haɓakar haɓakar PDH phosphorylation mai mahimmanci ta PDH kinase 3. Daidaita da lura a cikin sel, nazarin bayanan TCGA ya nuna haɓakar ƙimar PC a cikin mutant IDH-bayyana samfuran glioma na ɗan adam idan aka kwatanta da daji- rubuta IDH.Bincikenmu ya nuna cewa canje-canje a cikin PC da PDH na iya zama muhimmin ɓangare na daidaitawar salula zuwa maye gurbin IDH1 kuma yana iya zama maƙasudin warkewa.