Ubushakashatsi buheruka gukorwa muri siyanse: Kuzuza spermidine birashobora kongera uburyo bwo kurwanya ibibyimba birwanya indwara
Ubudahangarwa bw'umubiri bugabanuka uko imyaka igenda ishira, kandi abantu bakuze bakunze kwibasirwa n'indwara na kanseri, kandi kubuza PD-1, imiti ikunze gukoreshwa, akenshi usanga bidakorwa neza ku bantu bakuze kuruta mu rubyiruko. Ubushakashatsi bwerekanye ko muri spermidine ya biologiya polyamine igabanuka uko imyaka igenda ishira, kandi kuzuza spermidine birashobora kunoza cyangwa gutinza indwara zimwe na zimwe ziterwa nimyaka, harimo n'indwara z'umubiri. Nyamara, isano iri hagati yo kubura intanga ngabo iherekeza gusaza hamwe na senescence iterwa na immunosuppression T selile.
Vuba aha, abashakashatsi bo muri kaminuza ya Kyoto yo mu Buyapani basohoye inyandiko y’ubushakashatsi bise “Spermidine ikora poroteyine ya mitochondial kandi ikora ubudahangarwa bw'umubiri mu mbeba” muri siyansi. Ubu bushakashatsi bugaragaza ko intanga ngabo ihuza kandi igakora poroteyine MTP ya mitochondrial trifonctionnement MTP, igatera okiside ya aside irike, kandi amaherezo iganisha ku mikorere ya mitochondial metabolisme muri selile CD8 + T kandi igatera ubudahangarwa bw'umubiri. Ibisubizo byerekanye ko kuvura hamwe na spermidine hamwe na antibody anti-PD-1 byongereye ikwirakwizwa, umusaruro wa cytokine hamwe na ATP ya mitochondrial ATP ikora selile CD8 + T, kandi spermidine yazamuye imikorere ya mitochondial kandi byongera cyane mitochondrial fatty aside okiside metabolisme mu isaha imwe.
Kugira ngo hamenyekane niba spermidine ikora mu buryo butaziguye aside irike (FAO) muri mitochondriya, itsinda ry’ubushakashatsi ryagenwe n’isesengura ry’ibinyabuzima ryerekana ko spermidine ihuza na poroteyine ya mitochondial (MTP), enzyme yo hagati muri aside irike β-okiside. MTP igizwe na α na un subunits, byombi bihuza spermidine. Ubushakashatsi bwakoresheje MTPs bwashizwe hamwe kandi bwezwa muri E. coli bwerekanye ko spermidine ihuza MTPs hamwe n’ubufatanye bukomeye [guhuza isano (gutandukana, Kd) = 0.1 μM] kandi byongera ibikorwa bya okiside ya aside irike. Kugabanuka kwihariye kwa MTPα muri selile T yakuyeho ingaruka za spermidine kuri PD-1-ikingira immunotherapy, byerekana ko MTP isabwa kugirango spermidine iterwa na selile.
Mu gusoza, spermidine yongerera aside aside mu guhuza no gukora MTP. Kwiyongera hamwe na spermidine birashobora kongera ibikorwa bya okiside ya aside irike, kunoza ibikorwa bya mitochondial hamwe na cytotoxic ya selile CD8 + T. Itsinda ry’ubushakashatsi rifite imyumvire mishya y’imiterere ya spermidine, ishobora gufasha mu gushyiraho ingamba zo gukumira no kunoza ingaruka z’indwara ziterwa n’imyaka ndetse no kurwanya kutitabira imiti ivura indwara ya PD-1 ititaye ku myaka.
Igihe cyo kohereza: Gashyantare-27-2023
