Kev tshawb fawb zaum kawg hauv Kev Tshawb Fawb: Ntxiv spermidine tuaj yeem txhim kho cov txheej txheem ntawm kev tiv thaiv qog noj ntshav.

 Kev tshawb fawb zaum kawg hauv Kev Tshawb Fawb: Ntxiv spermidine tuaj yeem txhim kho cov txheej txheem ntawm kev tiv thaiv qog noj ntshav.

  Lub cev tiv thaiv kab mob poob qis thaum muaj hnub nyoog, thiab cov neeg laus muaj kev cuam tshuam ntau dua rau kev kis kab mob thiab mob qog noj ntshav, thiab PD-1 inhibition, kev kho mob feem ntau tsis zoo rau cov neeg laus dua li cov neeg hluas. Cov kev tshawb fawb tau pom tias muaj cov kab mob polyamine spermidine hauv tib neeg lub cev uas txo qis nrog lub hnub nyoog, thiab kev ntxiv nrog cov spermidine tuaj yeem txhim kho lossis ncua qee cov kab mob uas muaj hnub nyoog, suav nrog cov kab mob hauv lub cev. Txawm li cas los xij, kev sib raug zoo ntawm spermidine deficiency uas nrog rau kev laus thiab kev qaug zog ntawm T cell immunosuppression tsis meej.

Tsis ntev los no, cov kws tshawb fawb los ntawm Kyoto University hauv Nyij Pooj tau luam tawm cov ntawv tshawb fawb hu ua "Spermidine activates mitochondrial trifunctional protein thiab txhim kho cov tshuaj tiv thaiv kab mob hauv nas" hauv Science. Txoj kev tshawb no qhia tau hais tias spermidine ncaj qha khi thiab ua kom cov mitochondrial trifunctional protein MTP, ua rau fatty acid oxidation, thiab thaum kawg ua rau txhim kho mitochondrial metabolism hauv CD8+ T hlwb thiab txhawb kev tiv thaiv qog nqaij hlav. Cov txiaj ntsig tau pom tias kev kho mob ua ke nrog spermidine thiab anti-PD-1 antibody txhim kho qhov kev loj hlob, cytokine ntau lawm thiab mitochondrial ATP zus tau tej cov CD8+ T hlwb, thiab spermidine zoo txhim kho mitochondrial muaj nuj nqi thiab nce mitochondrial fatty acid oxidation metabolism hauv 1 teev.

Txhawm rau tshawb xyuas seb spermidine ncaj qha ua rau cov kua qaub oxidase (FAO) hauv mitochondria, pab pawg tshawb fawb tau txiav txim siab los ntawm kev tshuaj xyuas biochemical uas spermidine khi rau mitochondrial trifunctional protein (MTP), lub hauv paus enzyme hauv fatty acid β-oxidation. MTP muaj α thiab β subunits, ob qho tib si khi spermidine. Kev sim siv MTPs synthesized thiab purified los ntawm E. coli pom tias spermidine khi MTPs nrog muaj zog affinity [binding affinity (dissociation tas li, Kd) = 0.1 μM] thiab txhim kho lawv cov enzymatic fatty acid oxidation kev ua. Qhov tshwj xeeb depletion ntawm MTPα subunit hauv T hlwb tshem tawm cov txiaj ntsig zoo ntawm spermidine ntawm PD-1-suppressive immunotherapy, qhia tias MTP yuav tsum muaj rau spermidine-dependent T cell activation.

Hauv kev xaus, spermidine txhim kho fatty acid oxidation los ntawm kev khi ncaj qha thiab ua kom MTP. Ntxiv nrog rau spermidine tuaj yeem txhim kho fatty acid oxidation kev ua haujlwm, txhim kho mitochondrial kev ua haujlwm thiab cytotoxic muaj nuj nqi ntawm CD8 + T hlwb. Pab neeg tshawb fawb muaj kev nkag siab tshiab ntawm cov khoom ntawm spermidine, uas tuaj yeem pab tsim cov tswv yim los tiv thaiv thiab txhim kho cov txiaj ntsig ntawm hnub nyoog tiv thaiv kab mob thiab tiv thaiv tsis ua hauj lwm rau PD-1 inhibitory therapy hauv kev mob qog noj ntshav, tsis hais hnub nyoog li cas.