Nchọpụta kachasị ọhụrụ na Sayensị: Ịtinye spermidine nwere ike ịkwalite usoro nzaghachi mgbochi tumor

 Nchọpụta kachasị ọhụrụ na Sayensị: Ịtinye spermidine nwere ike ịkwalite usoro nzaghachi mgbochi tumor

  Usoro ahụ ji alụso ọrịa ọgụ na-ebelata ka afọ, na ndị agadi na-enwekarị ike ibute ọrịa na ọrịa cancer, yana mgbochi PD-1, ọgwụgwọ a na-ejikarị eme ihe, adịghị adị irè na ndị agadi karịa ndị na-eto eto. Nnyocha egosiwo na e nwere polyamine spermidine dị ndụ na ahụ mmadụ nke na-ebelata na afọ, na mgbakwunye na spermidine nwere ike imeziwanye ma ọ bụ gbuo oge ụfọdụ ọrịa ndị metụtara afọ, gụnyere ọrịa na-alụso ọrịa ọgụ. Otú ọ dị, mmekọrịta dị n'etiti ụkọ spermidine nke na-esonyere ịka nká na nkwụsị nke immunosuppression T cell nke senescence kpatara amabeghị.

N'oge na-adịbeghị anya, ndị nchọpụta sitere na Mahadum Kyoto dị na Japan bipụtara akwụkwọ nyocha nke isiokwu ya bụ "Spermidine na-arụ ọrụ protein trifunctional mitochondrial ma na-eme ka mgbochi antitumor na ụmụ oke" dị na Sayensị. Ọmụmụ ihe a na-ekpughe na spermidine na-ejikọta kpọmkwem ma na-arụ ọrụ protein trifunctional mitochondrial MTP, na-akpalite fatty acid oxidation, na n'ikpeazụ na-eduga ná nkwalite mitochondrial metabolism na CD8+ T cell na-akwalite mgbochi tumor immunity. Nsonaazụ gosiri na ngwakọta ọgwụgwọ na spermidine na mgbochi PD-1 kwalitere mmụba, mmepụta cytokine na mmepụta mitochondrial ATP nke mkpụrụ ndụ CD8+ T, na spermidine kwalitere ọrụ mitochondrial nke ọma ma mụbaa mitochondrial fatty acid oxidation metabolism n'ime awa 1.

Iji chọpụta ma spermidine ọ na-arụ ọrụ fatty acid oxidase (FAO) ozugbo na mitochondria, otu nyocha ahụ kpebiri site na nyocha biochemical na spermidine na-ejikọta protein trifunctional mitochondrial (MTP), enzyme Central na fatty acid β-oxidation. MTP nwere α na β subunits, ha abụọ na-ejikọta spermidine. Nlele na-eji MTP arụpụtara ma dị ọcha site na E. coli gosiri na spermidine na-ejikọta MTP na njikọ siri ike [binding affinity (dissociation constant, Kd) = 0.1 μM] ma na-eme ka ọrụ oxidation fatty acid ha dịkwuo elu. Mbelata nke akụkụ MTPa dị na mkpụrụ ndụ T kagburu mmetụta ike nke spermidine na PD-1-suppressive immunotherapy, na-atụ aro na MTP chọrọ maka spermidine-based T cell activation.

N'ikpeazụ, spermidine na-eme ka oxidation fatty acid dịkwuo mma site na ijikọ na ịgbalite MTP. Mgbakwunye na spermidine nwere ike ịkwalite ọrụ oxidation fatty acid, melite ọrụ mitochondrial na ọrụ cytotoxic nke sel CD8+ T. Ndị otu nyocha ahụ nwere nghọta ọhụrụ nke njirimara nke spermidine, nke nwere ike inye aka mepụta atụmatụ iji gbochie ma melite nsonaazụ nke ọrịa mgbochi afọ na ịlụ ọgụ na-anabataghị ọgwụgwọ PD-1 inhibitory na ọrịa cancer, n'agbanyeghị afọ ole.