ʻO ka noiʻi hou loa i ka ʻepekema: ʻO ka hoʻohui ʻana i ka spermidine hiki ke hoʻonui i ke ʻano o ka pane ʻana i ka anti-tumor

 ʻO ka noiʻi hou loa i ka ʻepekema: ʻO ka hoʻohui ʻana i ka spermidine hiki ke hoʻonui i ke ʻano o ka pane ʻana i ka anti-tumor

  Ke emi nei ka ʻōnaehana pale i ka makahiki, a ʻoi aku ka maʻalahi o ka poʻe ʻelemakule i nā maʻi a me nā maʻi maʻi, a ʻo ka PD-1 inhibition, kahi lapaʻau maʻamau, ʻoi aku ka maikaʻi o ka poʻe ʻelemakule ma mua o ka poʻe ʻōpio. Ua hōʻike nā haʻawina aia kahi spermidine polyamine biological i loko o ke kino o ke kanaka e emi ana me ka makahiki, a hiki i ka hoʻohui ʻana me ka spermidine ke hoʻomaikaʻi a hoʻopaneʻe paha i kekahi mau maʻi pili makahiki, me nā maʻi ʻōnaehana pale. Eia naʻe, ʻaʻole maopopo ka pilina ma waena o ka spermidine deficiency e pili ana i ka ʻelemakule a me ka senescence-induced T cell immunosuppression.

I kēia mau lā, ua paʻi nā mea noiʻi mai ke Kulanui ʻo Kyoto ma Iapana i kahi pepa noiʻi i kapa ʻia ʻo "Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice" in Science. Hōʻike kēia haʻawina e hoʻopaʻa pololei a hoʻōla ka spermidine i ka mitochondrial trifunctional protein MTP, e hoʻoulu ai i ka hoʻoheheʻe ʻana i ka momona momona, a i ka hopena e alakaʻi i ka hoʻonui mitochondrial metabolism i nā CD8 + T cell a paipai i ka pale anti-tumor. Ua hōʻike nā hopena i ka hui pū ʻana me ka spermidine a me ka anti-PD-1 antibody i hoʻonui i ka proliferation, cytokine production a me ka mitochondrial ATP production o CD8 + T cell, a me ka spermidine i hoʻomaikaʻi maikaʻi i ka hana mitochondrial a hoʻonui nui i ka mitochondrial fatty acid oxidation metabolism i loko o 1 hola.

No ka ʻimi ʻana inā hoʻāla pololei ka spermidine i ka fatty acid oxidase (FAO) i ka mitochondria, ua hoʻoholo ka hui noiʻi e ka loiloi biochemical e hoʻopaʻa ai ka spermidine i ka mitochondrial trifunctional protein (MTP), kahi enzyme kikowaena i loko o ka fatty acid β-oxidation. Aia ka MTP i nā subunits α a me β, nā mea ʻelua e hoʻopaʻa i ka spermidine. ʻO nā hoʻokolohua me ka hoʻohana ʻana i nā MTP i hoʻohui ʻia a hoʻomaʻemaʻe ʻia mai E. coli i hōʻike ʻia e hoʻopaʻa ʻia ka spermidine i nā MTP me ka pilina ikaika [pili pili (dissociation mau, Kd) = 0.1 μM] a hoʻonui i kā lākou enzymatic fatty acid oxidation hana. ʻO ka hoʻohaʻahaʻa kikoʻī o ka MTPα subunit i loko o nā pūnaewele T i hoʻopau i ka hopena potentiation o spermidine ma PD-1-suppressive immunotherapy, e hōʻike ana e koi ʻia ʻo MTP no ka hoʻoulu ʻana o ka cell T cell spermidine.

I ka hopena, hoʻonui ka spermidine i ka oxidation fatty acid ma o ka hoʻopaʻa pololei ʻana a me ka hoʻoulu ʻana i ka MTP. Hiki i ka hoʻohui ʻana me ka spermidine ke hoʻoikaika i ka hana hoʻomake ʻana o ka waikawa momona, hoʻomaikaʻi i ka hana mitochondrial a me ka hana cytotoxic o nā cell CD8 + T. Loaʻa i ka hui noiʻi kahi ʻike hou i nā waiwai o ka spermidine, hiki ke kōkua i ka hoʻomohala ʻana i nā hoʻolālā e pale a hoʻomaikaʻi i ka hopena o nā maʻi kūlohelohe pili makahiki a me ka hakakā ʻana i ka pane ʻole i ka PD-1 inhibitory therapy i ka maʻi kanesa, me ka ʻole o ka nui o ka makahiki.