000118921 001__ 118921
000118921 005__ 20240319081008.0
000118921 0247_ $$2doi$$a10.3390/ijms23158705
000118921 0248_ $$2sideral$$a130035
000118921 037__ $$aART-2022-130035
000118921 041__ $$aeng
000118921 100__ $$aSoler Agesta, R.$$uUniversidad de Zaragoza
000118921 245__ $$aConjugation of the 9-kDa isoform of Granulysin with liposomes potentiates its cytotoxicity
000118921 260__ $$c2022
000118921 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118921 5203_ $$aNine kDa granulysin (GRNLY) is a human cytolytic protein secreted by cytotoxic T lymphocytes (CTL) and NK cells of the immune system whose demonstrated physiological function is the elimination of bacteria and parasites. In previous studies by our group, the anti-tumor capacity of recombinant granulysin was demonstrated, both in vitro and in vivo. In the present work, we developed lipid nanoparticles whose surfaces can bind recombinant granulysin through the formation of a complex of coordination between the histidine tail of the protein and Ni2+ provided by a chelating lipid in the liposome composition and termed them LUV-GRNLY, for granulysin-bound large unilamellar vesicles. The objective of this formulation is to increase the granulysin concentration at the site of contact with the target cell and to increase the cytotoxicity of the administered dose. The results obtained in this work indicate that recombinant granulysin binds to the surface of the liposome with high efficiency and that its cytotoxicity is significantly increased when it is in association with liposomes. In addition, it has been demonstrated that the main mechanism of death induced by both granulysin and LUV-GRNLY is apoptosis. Jurkat-shBak cells are resistant to GRNLY and also to LUV-GRNLY, showing that LUV-GRNLY uses the mitochondrial apoptotic pathway to induce cell death. On the other hand, we show that LUV-GRNLY induces the expression of the pro-apoptotic members of the Bcl-2 family Bim and especially PUMA, although it also induced the expression of anti-apoptotic Bcl-xL. In conclusion, we demonstrate that binding of GRNLY to the surfaces of liposomes clearly augments its cytotoxic potential, with cell death executed mainly by the mitochondrial apoptotic pathway.
000118921 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
000118921 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000118921 590__ $$a5.6$$b2022
000118921 592__ $$a1.154$$b2022
000118921 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b66 / 285 = 0.232$$c2022$$dQ1$$eT1
000118921 593__ $$aMedicine (miscellaneous)$$c2022$$dQ1
000118921 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b52 / 178 = 0.292$$c2022$$dQ2$$eT1
000118921 593__ $$aPhysical and Theoretical Chemistry$$c2022$$dQ1
000118921 593__ $$aComputer Science Applications$$c2022$$dQ1
000118921 593__ $$aInorganic Chemistry$$c2022$$dQ1
000118921 593__ $$aSpectroscopy$$c2022$$dQ1
000118921 593__ $$aOrganic Chemistry$$c2022$$dQ1
000118921 593__ $$aMolecular Biology$$c2022$$dQ2
000118921 593__ $$aCatalysis$$c2022$$dQ2
000118921 594__ $$a7.8$$b2022
000118921 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000118921 700__ $$0(orcid)0000-0002-1657-4792$$aGuerrero-Ochoa, P.$$uUniversidad de Zaragoza
000118921 700__ $$aMarco-Brualla, J.$$uUniversidad de Zaragoza
000118921 700__ $$aIbáñez-Pérez, R.
000118921 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, I.$$uUniversidad de Zaragoza
000118921 700__ $$0(orcid)0000-0003-3043-147X$$aMartínez Lostao, L.$$uUniversidad de Zaragoza
000118921 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza
000118921 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000118921 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000118921 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000118921 773__ $$g23, 15 (2022), 8705 [13 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000118921 8564_ $$s1981037$$uhttps://zaguan.unizar.es/record/118921/files/texto_completo.pdf$$yVersión publicada
000118921 8564_ $$s2649865$$uhttps://zaguan.unizar.es/record/118921/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000118921 909CO $$ooai:zaguan.unizar.es:118921$$particulos$$pdriver
000118921 951__ $$a2024-03-18-14:50:13
000118921 980__ $$aARTICLE