Kafukufuku waposachedwa mu Science: Supplementing spermidine amatha kupititsa patsogolo njira ya anti-chotupa immune reaction

 Kafukufuku waposachedwa mu Science: Supplementing spermidine amatha kupititsa patsogolo njira ya anti-chotupa immune reaction

  Chitetezo cha mthupi chimachepa ndi ukalamba, ndipo anthu okalamba amatha kutenga matenda ndi khansa, ndipo PD-1 inhibition, mankhwala omwe amagwiritsidwa ntchito kwambiri, nthawi zambiri sagwira ntchito kwa okalamba kusiyana ndi achinyamata. Kafukufuku wasonyeza kuti pali biological polyamine spermidine mu thupi la munthu amene amachepetsa ndi zaka, ndi supplementation ndi spermidine akhoza kusintha kapena kuchedwetsa matenda ena okhudzana ndi ukalamba, kuphatikizapo matenda a chitetezo cha m'thupi. Komabe, mgwirizano pakati pa kusowa kwa spermidine komwe kumayenderana ndi ukalamba ndi senescence-induced T cell immunosuppression sichidziwika bwino.

Posachedwapa, ofufuza ochokera ku yunivesite ya Kyoto ku Japan adafalitsa pepala lofufuzira lotchedwa "Spermidine imayendetsa mapuloteni a mitochondrial trifunctional ndipo imapangitsa kuti chitetezo cha mthupi chitetezeke mu mbewa" mu Science. Kafukufukuyu akuwonetsa kuti spermidine imamanga mwachindunji ndikuyambitsa puloteni ya mitochondrial trifunctional MTP, imayambitsa mafuta acid oxidation, ndipo pamapeto pake imayambitsa kupititsa patsogolo kagayidwe ka mitochondrial m'maselo a CD8 + T ndikulimbikitsa chitetezo chamthupi chotsutsana ndi chotupa. Zotsatira zinasonyeza kuti mankhwala ophatikizana ndi spermidine ndi anti-PD-1 antibody anawonjezera kuchulukana, kupanga cytokine ndi mitochondrial ATP kupanga maselo a CD8 + T, ndipo spermidine imathandizira bwino ntchito ya mitochondrial ndikuwonjezera kwambiri mitochondrial mafuta acid oxidation metabolism mkati mwa ola limodzi.

Kufufuza ngati spermidine imayambitsa mwachindunji mafuta acid oxidase (FAO) mu mitochondria, gulu lofufuza lodziwika ndi biochemical analysis kuti spermidine imamangiriza ku mitochondrial trifunctional protein (MTP), puloteni yapakati mu mafuta acid β-oxidation. MTP imakhala ndi ma subunits a α ndi β, onse omwe amamanga spermidine. Kuyesera pogwiritsa ntchito MTPs kupangidwa ndi kuyeretsedwa kuchokera ku E. coli kunasonyeza kuti spermidine imamangiriza MTPs ndi mgwirizano wamphamvu [kumanga mgwirizano (dissociation constant, Kd) = 0.1 μM] ndikuwonjezera ntchito yawo ya enzymatic fatty acid oxidation. Kuchepa kwapadera kwa subunit ya MTPα m'maselo a T kunachotsa mphamvu ya spermidine pa PD-1-suppressive immunotherapy, kutanthauza kuti MTP ndiyofunika kuti spermidine-amadalira T cell activation.

Pomaliza, spermidine kumawonjezera mafuta asidi makutidwe ndi okosijeni mwa mwachindunji kumanga ndi yambitsa MTP. Kuphatikizika ndi spermidine kumatha kupititsa patsogolo ntchito ya okosijeni yamafuta acid, kupititsa patsogolo ntchito ya mitochondrial ndi ntchito ya cytotoxic ya ma CD8+ T. Gulu lofufuzira liri ndi chidziwitso chatsopano cha katundu wa spermidine, zomwe zingathandize kupanga njira zopewera ndi kupititsa patsogolo zotsatira za matenda okhudzana ndi ukalamba komanso kuthana ndi kusagwirizana ndi PD-1 mankhwala oletsa khansa, mosasamala kanthu za kukula kwa msinkhu.