Lipatlisiso tsa morao-rao ho Saense: Ho tlatsetsa spermidine ho ka ntlafatsa mochine oa karabelo ea 'mele ea ho itšireletsa mafung
Tsamaiso ea 'mele ea ho itšireletsa mafung e fokotseha ha lilemo li ntse li hōla,' me batho ba hōlileng ba kotsing ea ho tšoaetsoa mafu le kankere, 'me thibelo ea PD-1, e leng phekolo e sebelisoang hangata, hangata ha e sebetse ho batho ba baholo ho feta ho batho ba bacha. Liphuputso li bontšitse hore ho na le biological polyamine spermidine 'meleng oa motho e fokotsehang ka lilemo,' me tlatsetso e nang le spermidine e ka ntlafatsa kapa ea liehisa mafu a mang a amanang le lilemo, ho akarelletsa le mafu a tsamaiso ea 'mele ea ho itšireletsa mafung. Leha ho le joalo, kamano pakeng tsa khaello ea spermidine e tsamaeang le botsofali le senescence-induced T cell immunosuppression ha e hlake.
Haufinyane tjena, bafuputsi ba Univesithi ea Kyoto e Japane ba phatlalalitse pampiri ea lipatlisiso e nang le sehlooho se reng "Spermidine e kenya tšebetsong protheine ea mitochondrial trifunctional mme e ntlafatsa ho itšireletsa mafung ho litoeba" ho Saense. Boithuto bona bo senola hore spermidine e tlama le ho kenya tšebetsong protheine ea mitochondrial trifunctional MTP, e baka oxidation ea mafura a acid, 'me qetellong e lebisa ntlafatsong ea metabolism ea mitochondrial liseleng tsa CD8 + T mme e khothalletsa ho itšireletsa mafung. Liphello li bontšitse hore phekolo e kopantsoeng le spermidine le anti-PD-1 antibody e matlafalitse ho ata, tlhahiso ea cytokine le tlhahiso ea mitochondrial ATP ea lisele tsa CD8 + T, 'me spermidine e atlehile ho ntlafatsa mosebetsi oa mitochondrial' me e ekelitse haholo mitochondrial fatty acid oxidation metabolism nakong ea 1 hora.
Ho hlahloba hore na spermidine e sebetsa ka ho toba mafura a acid oxidase (FAO) ho mitochondria, sehlopha sa lipatlisiso se khethiloeng ke tlhahlobo ea lik'hemik'hale tsa biochemical hore spermidine e tlama ho mitochondrial trifunctional protein (MTP), e leng enzyme e bohareng ea mafura a acid β-oxidation. MTP e na le likaroloana tsa α le β, tseo ka bobeli li tlamang spermidine. Liteko tse sebelisang li-MTP tse entsoeng le ho hloekisoa ho tloha ho E. coli li bontšitse hore spermidine e tlama li-MTP ka kamano e matla [tlamahano e tlamang (dissociation constant, Kd) = 0.1 μM] le ho ntlafatsa mosebetsi oa bona oa enzymatic fatty oxidation. Ho fokotseha ho hoholo ha karoloana ea MTPα liseleng tsa T ho hlakotse phello e ka bang teng ea spermidine ho PD-1-suppressive immunotherapy, e fana ka maikutlo a hore MTP e hlokahala bakeng sa ts'ebetso ea T cell e itšetlehileng ka spermidine.
Qetellong, spermidine e ntlafatsa mafura a acid oxidation ka ho tlama le ho kenya MTP ka ho toba. Ho tlatselletsa ka spermidine ho ka ntlafatsa ts'ebetso ea oxidation ea mafura a mafura, ho ntlafatsa ts'ebetso ea mitochondrial le ts'ebetso ea cytotoxic ea lisele tsa CD8 + T. Sehlopha sa lipatlisiso se na le kutloisiso e ncha ea thepa ea spermidine, e ka thusang ho hlahisa mekhoa ea ho thibela le ho ntlafatsa sephetho sa mafu a ho itšireletsa mafung a amanang le lilemo le ho loantša ho se arabele ho PD-1 inhibitory therapy ka kankere, ho sa tsotellehe boholo ba lilemo.
Nako ea poso: Feb-27-2023
