Ucwaningo lwakamuva lweSayensi: Ukwengeza i-spermidine kungathuthukisa indlela yokusabela kwe-anti-tumor immune immune
Amasosha omzimba ayancipha ngokuya ngeminyaka, futhi abantu abadala bangenwa kalula izifo kanye nomdlavuza, futhi inhibition ye-PD-1, ukwelashwa okuvame ukusetshenziswa, ngokuvamile ayisebenzi kahle kubantu abadala kunasebancane. Ucwaningo luye lwabonisa ukuthi kukhona i-polyamine spermidine ye-biological emzimbeni womuntu eyancipha ngokukhula, futhi ukufakwa kwe-spermidine kungathuthukisa noma kubambezele ezinye izifo ezihlobene neminyaka, kuhlanganise nezifo zesistimu yomzimba. Kodwa-ke, ubudlelwano phakathi kokuntuleka kwe-spermidine okuhambisana nokuguga kanye ne-senescence-induced T cell immunosuppression akucaci.
Muva nje, abacwaningi abavela eNyuvesi yaseKyoto eJapane bashicilele iphepha lokucwaninga elinesihloko esithi "Spermidine activates mitochondrial trifunctional protein and improves antitumor immune in amagundane" kuSayensi. Lolu cwaningo lwembula ukuthi i-spermidine ibopha ngokuqondile futhi yenze iphrotheni ye-mitochondrial trifunctional MTP, ivuse i-fatty acid oxidation, futhi ekugcineni iholele ekuthuthukisweni kwemetabolism ye-mitochondrial kumaseli e-CD8+ T futhi ikhuthaze ukungatheleleki kwe-tumor. Imiphumela yabonisa ukuthi ukwelashwa okuhlangene ne-spermidine kanye ne-anti-PD-1 antibody kwathuthukisa ukwanda, ukukhiqizwa kwe-cytokine kanye nokukhiqizwa kwe-ATP ye-mitochondrial yamaseli e-CD8 + T, futhi i-spermidine ithuthukise ngempumelelo umsebenzi we-mitochondrial futhi yandisa kakhulu i-mitochondrial fatty acid oxidation metabolism phakathi nehora elingu-1.
Ukuhlola ukuthi ingabe i-spermidine iyenza isebenze ngokuqondile i-fatty acid oxidase (FAO) ku-mitochondria, ithimba locwaningo elinqunywe ngokuhlaziywa kwe-biochemical ukuthi i-spermidine ibophezela ku-mitochondrial trifunctional protein (MTP), i-enzyme emaphakathi ku-β-oxidation ye-fatty acid. I-MTP iqukethe ama-subunits angu-α kanye no-β, womabili abopha i-spermidine. Ukuhlola okusebenzisa ama-MTP ahlanganisiwe futhi ahlanjululwa ku-E. coli kubonise ukuthi i-spermidine ibopha ama-MTP ngokuhlangana okuqinile [ukubopha okuhambisanayo (i-dissociation constant, Kd) = 0.1 μM] futhi ithuthukisa umsebenzi wabo we-enzymatic fatty oxidation. Ukwehliswa okuqondile kwe-subunit ye-MTPα kumaseli e-T kuhoxise umphumela onamandla we-spermidine ku-PD-1-suppressive immunotherapy, okuphakamisa ukuthi i-MTP iyadingeka ukuze kusebenze i-T cell encike ku-spermidine.
Ekuphetheni, i-spermidine ithuthukisa i-fatty acid oxidation ngokubopha ngokuqondile nokusebenzisa i-MTP. Ukwengeza nge-spermidine kungathuthukisa umsebenzi we-fatty acid oxidation, kuthuthukise umsebenzi we-mitochondrial kanye nomsebenzi we-cytotoxic wamaseli e-CD8+ T. Ithimba locwaningo linokuqonda okusha kwezakhiwo ze-spermidine, ezingasiza ekuthuthukiseni amasu okuvimbela nokuthuthukisa umphumela wezifo zokuzivikela ezihlobene neminyaka kanye nokulwa nokungaphenduli ku-PD-1 yokwelapha evimbela umdlavuza, kungakhathaliseki ukuthi ungakanani ubudala.
Isikhathi sokuthumela: Feb-27-2023
