Tsvagiridzo yazvino muSainzi: Kuwedzera spermidine kunogona kusimudzira magadzirirwo ekurwisa-tumor immune immune
Masoja ekudzivirira emuviri anoderera nezera, uye vanhu vakura vanotapukirwa nehutachiona nekenza, uye PD-1 inhibition, kurapwa kunowanzoshandiswa, kazhinji haishande muvanhu vakura kupfuura mune vechidiki. Zvidzidzo zvakaratidza kuti kune biological polyamine spermidine mumuviri wemunhu inoderera nezera, uye kuwedzera ne spermidine kunogona kuvandudza kana kunonoka zvimwe zvirwere zvine chekuita nezera, kusanganisira immune system zvirwere. Nekudaro, hukama pakati pekushomeka kwespermidine kunoenderana nekuchembera uye senescence-induced T cell immunosuppression haina kujeka.
Munguva ichangopfuura, vatsvakurudzi veKyoto University muJapan vakabudisa tsvakurudzo bepa rine musoro unoti "Spermidine activates mitochondrial trifunctional protein uye inovandudza antitumor immunity mumakonzo" muSainzi. Ichi chidzidzo chinoburitsa kuti spermidine inosunga zvakananga uye inomisa iyo mitochondrial trifunctional protein MTP, inokonzeresa fatty acid oxidation, uye pakupedzisira inotungamira kukwidziridzwa mitochondrial metabolism muCD8+ T masero uye inosimudzira anti-bundu kusadzivirirwa. Zvigumisiro zvakaratidza kuti kurapwa kwakabatanidzwa ne spermidine uye anti-PD-1 antibody kwakasimudzira kuwedzera, kugadzirwa kwe cytokine uye mitochondrial ATP kugadzirwa kweCD8 + T masero, uye spermidine inobudirira inovandudza mitochondrial basa uye zvakanyanya kuwedzera mitochondrial fatty acid oxidation metabolism mukati meawa 1.
Kuongorora kana spermidine inobata zvakananga fatty acid oxidase (FAO) mumitochondria, boka rekutsvagisa rakatemerwa nekuongorora kwebiochemical iyo spermidine inosunga kune mitochondrial trifunctional protein (MTP), iyo yepakati enzyme mu fatty acid β-oxidation. MTP ine α uye β subunits, ose anosunga spermidine. Miedzo inoshandisa MTPs yakagadzirwa uye yakacheneswa kubva kuE. coli yakaratidza kuti spermidine inosunga MTPs nekubatana kwakasimba [kusunga hukama (dissociation constant, Kd) = 0.1 μM] uye inowedzera enzymatic fatty acid oxidation yavo. Kunyatsopera kweMTPa subunit muT masero akabvisa simba rekuita respermidine paPD-1-suppressive immunotherapy, zvichiratidza kuti MTP inodiwa kuti spermidine-inotenderera T cell activation.
Mukupedzisa, spermidine inowedzera fatty acid oxidation nekusunga zvakananga nekuita MTP. Kuwedzera ne spermidine kunogona kusimudzira fatty acid oxidation chiitiko, kunatsiridza mitochondrial chiitiko uye cytotoxic basa reCD8+ T masero. Boka rekutsvagisa rine kunzwisisa kutsva kwezvinhu zve spermidine, izvo zvinogona kubatsira kugadzira nzira dzekudzivirira nekuvandudza mhedzisiro yezvirwere zvine chekuita nezera uye kurwisa kusapindura kune PD-1 inhibitory therapy mugomarara, zvisinei nekukura kwezera.
Nguva yekutumira: Feb-27-2023
