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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoglobal.org-2Findex.php-2FMITOEAGLE-7CCOST-20Action-20MITOEAGLE-5D-5D-0AAdenylate-20kinase-20(AK)-20is-20a-20ubiquitous-20enzyme-20critical-20in-20intracellular-20energy-20transfer-20processes,-20the-20maintenance-20of-20energy-20homeostasis,-20and-20a-20major-20player-20in-20AMP-20metabolic-20signaling-20circuits-20in-20some-20highly-20differentiated-20cells.-20However,-20the-20role-20of-20the-20AK-20network-20in-20aging,-20during-20cancerogenesis-20is-20poorly-20understood.-20The-20main-20limitation-20in-20research-20of-20the-20AK-20network-20is-20that-20cytosolic-20and-20mitochondrial-20AK-20metabolic-20flux-20cannot-20be-20separated-20due-20to-20the-20absence-20of-20isoform-20specific-20inhibitor.-0A-0AFor-20this-20purpose,-20a-20simple-20oxygraphic-20method-20was-20developed-20that-20enables-20directly-20and-20semi-2Dquantitatively-20estimate-20the-20distribution-20between-20cytosolic-20AK1-20and-20mitochondrial-20AK2-20localized-20in-20the-20intermembrane-20space,-20both-20in-20isolated-20cells-20and-20tissue-20samples-20(biopsy-20material).-20Experiments-20were-20performed-20on-20isolated-20rat-20mitochondria-20or-20permeabilized-20material,-20including-20undifferentiated-20and-20differentiated-20neuroblastoma-20Neuro-2D2a-20cells,-20pluripotent-20human-20embryonic-20stem-20cells,-20relatively-20null-20potent-20embryonal-20carcinoma-20cells-20(2102Ep-20cells-20line),-20HL-2D1-20cells,-20isolates-20rat-20heart-20cardiomyocytes-20(CM)-20as-20well-20as-20on-20human-20colorectal-20and-20breast-20cancer-20postoperative-20samples.-0A-0AIntracellular-20distribution-20of-20AK1-20and-20AK2-20can-20be-20detected-20by-20high-2Dresolution-20respirometry-20due-20to-20their-20functional-20coupling-20with-20ATP-20synthesis-20in-20mitochondria.-20Extracellular-20ADP-20which-20is-20not-20related-20to-20AK-20flux-20was-20eliminated-20by-20pyruvate-20kinase-20and-20its-20substrate-20phosphoenolpyruvate-20to-20ensure-20specific-20AK2-20functional-20coupling-20with-20mitochondria.-20Distribution-20of-20AK1-20and-20AK2-20is-20expressed-20by-20specific-20AK-20index.-20Our-20study-20showed-20that-20among-201-20year-20old-20rats-20total-20AK-20activity-20had-20already-20decreased-20in-20CM.-20Nevertheless,-20in-20all-20studied-20age-20groups-20no-20significant-20changes-20in-20AK1-20and-20AK2-20distribution-20were-20noticed.-20In-20ageing-20rat-20CMs-20it-20seems,-20that-20drastic-20alteration-20in-20CK-20network-20can-20be-20compensated-20by-20both-20AK1-20and-20AK2.-20Furthermore,-20in-20different-20cancer-20cell-20lines-20in-20contrast-20to-20the-20creatine-20kinase-20pathway,-20the-20AK-20phosphotransfer-20pathway-20is-20up-2Dregulated-20and-20the-20expression-20of-20AK2-20is-20higher-20than-20AK1-20in-20these-20malignant-20cells.-20The-20study-20of-20biopsy-20material-20showed-20that-20instead-20of-20mitochondrial-20creatine-20kinase-20the-20AK-20network-20was-20the-20main-20energy-20transfer-20pathway-20in-20colorectal-20and-20breast-20cancer.-20The-20respirometric-20method-20also-20revealed-20a-20considerable-20difference-20in-20mitochondrial-20affinity-20for-20AMP-20between-20nontransformed-20cells-20and-20tumor-20cells.-20-0A-0AIn-20summary,-20we-20developed-20a-20simple-20and-20rapid-20oxygraphic-20method-20to-20estimate-20semi-2Dquantitatively-20distribution-20of-20AK1-20and-20AK2-20in-20mammalian-20tissues-20and-20cultured-20cells.-20Our-20study-20showed-20that-20although,-20in-20aging-20rat-20CMs,-20the-20AK-20network-20slightly-20decreases,-20the-20AK1-20and-20AK2-20distribution-20remain-20unchanged.-20This-20method-20was-20tested-20also-20in-20cancer-20postoperative-20material-20and-20revealed-20that-20it-20was-20sensitive-20enough-20to-20perform-20on-20tumor-20biopsies.-20The-20data-20show-20that-20AK2-20highly-20expressed-20predominantly-20in-20poorly-20differentiated-20cells-20with-20a-20high-20proliferative-20index,-20and-20that-20strong-20differences-20exist-20between-20highly-2Ddifferentiated-20and-20tumor-20cells-20in-20the-20affinity-20of-20their-20mitochondrial-20respiration-20for-20exogenous-20AMP.-20Further-20studies-20will-20be-20required-20to-20identify-20the-20exact-20role-20of-20AK-20pathway-20in-20aging-20heart-20muscle-20and-20cancerogenesis." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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