Uphando lwakutsha nje kwiSayensi: Ukongeza i-spermidine kunokuphucula indlela yokusabela kwe-anti-tumor immune immune
Amajoni omzimba ayancipha ngenxa yobudala, kwaye abantu abadala banokuchaphazeleka ngakumbi kusulelo kunye nomhlaza, kunye ne-PD-1 inhibition, unyango olusetyenziswa ngokuqhelekileyo, luhlala lungasebenzi kakuhle kubantu abadala kunabancinci. Uphononongo lubonise ukuba kukho i-biological polyamine spermidine emzimbeni womntu eyancipha ngokukhula, kwaye ukuxhaswa nge-spermidine kunokuphucula okanye ukulibazisa ezinye izifo ezinxulumene neminyaka, kubandakanywa nezifo ze-immune system. Nangona kunjalo, ubudlelwane phakathi kokusilela kwe-spermidine okuhamba kunye nokuguga kunye ne-senescence-induced T cell immunosuppression akucaci.
Kutshanje, abaphandi abavela kwiYunivesithi yaseKyoto eJapan bapapashe iphepha lophando elinesihloko esithi "I-Spermidine isebenze iprotein ye-mitochondrial trifunctional kwaye iphucula i-antitumor immunity kwiimpuku" kwiSayensi. Olu phononongo lubonisa ukuba i-spermidine ibopha ngokuthe ngqo kwaye isebenze i-protein ye-mitochondrial trifunctional ye-MTP, ibangela i-oxidation ye-fatty acid, kwaye ekugqibeleni ikhokelela ekuphuculeni i-metabolism ye-mitochondrial kwiiseli ze-CD8 + T kwaye ikhuthaza ukugonywa kwe-anti-tumor. Iziphumo zibonise ukuba unyango oludibeneyo kunye ne-spermidine kunye ne-anti-PD-1 antibody yandisa ukwanda, ukuveliswa kwe-cytokine kunye nokuveliswa kwe-ATP ye-mitochondrial yeeseli ze-CD8 + T, kunye ne-spermidine iphucule ngokufanelekileyo umsebenzi we-mitochondrial kunye nokwandisa kakhulu i-mitochondrial fatty acid oxidation metabolism ngaphakathi kweyure ye-1.
Ukuphonononga ukuba i-spermidine isebenze ngokuthe ngqo kwi-fatty acid oxidase (FAO) kwi-mitochondria, iqela lophando elinqunywe luhlalutyo lwe-biochemical ukuba i-spermidine ibophelele kwiprotheni ye-mitochondrial trifunctional (MTP), i-enzyme ephakathi kwi-acid acid β-oxidation. I-MTP iqulathe ii-subunits ze-α kunye ne-β, zombini zibopha i-spermidine. Uvavanyo olusebenzisa i-MTPs edibeneyo kwaye ihlanjululwe kwi-E. coli ibonise ukuba i-spermidine ibophelela i-MTPs kunye nobudlelwane obuqinileyo [i-dissociation affinity (i-dissociation constant, Kd) = 0.1 μM] kwaye iphucula umsebenzi wabo we-enzymatic fatty oxidation. Ukuchithwa okuthe ngqo kwe-subunit ye-MTPα kwiiseli ze-T zacima impembelelo enokubakho ye-spermidine kwi-PD-1-suppressive immunotherapy, ebonisa ukuba i-MTP iyadingeka kwi-spermidine-exhomekeke kwi-T cell activation.
Ukuqukumbela, i-spermidine iphakamisa i-fatty acid oxidation ngokubopha ngokuthe ngqo kunye nokusebenza kwe-MTP. Ukongezwa nge-spermidine kunokunyusa umsebenzi we-fatty acid oxidation, ukuphucula umsebenzi we-mitochondrial kunye nomsebenzi we-cytotoxic weeseli ze-CD8 + T. Iqela lophando linokuqonda okutsha kweempawu ze-spermidine, ezinokunceda ukuphuhlisa izicwangciso zokuthintela nokuphucula umphumo wezifo ze-immune ezinxulumene neminyaka kunye nokulwa nokungaphenduli kwi-PD-1 yonyango lwe-inhibitory kwi-cancer, kungakhathaliseki ukuba ubudala.
Ixesha lokuposa: Feb-27-2023
