119999 20240319080946.0 doi 10.3390/ijms232113554 sideral 130930 ART-2022-130930 eng Moreno-Martinez, Laura Universidad de Zaragoza (orcid)0000-0002-7277-4318 Hemizygous Granzyme A Mice Expressing the hSOD1G93A Transgene Show Slightly Extended Lifespan 2022 Access copy available to the general public Unrestricted Granzyme A (gzmA), a serine protease involved in the modulation of the inflammatory immune response, is found at an elevated level in the serum from ALS patients. However, the influence of gzmA on the progression of ALS remains unclear. The aim of our work was to assess whether the absence of gzmA in an ALS murine model could help slow down the progression of the disease. Homozygous and hemizygous gzmA-deficient mice expressing the hSOD1G93A transgene were generated, and survival of these mice was monitored. Subsequently, gene and protein expression of inflammatory and oxidative stress markers was measured in the spinal cord and quadriceps of these mice. We observed the longest lifespan in gzmA+/− mice. GzmA gene and protein expression was downregulated in the spinal cord and serum from gmzA+/− mice, confirming that the increased survival of hemizygous mice is correlated with lower levels of gzmA. In addition, mRNA and protein levels of glutathione reductase (GSR), involved in oxidative stress, were found downregulated in the spinal cord and quadriceps of gmzA+/− mice, together with lower IL-1β and IL-6 mRNA levels in hemyzigous mice. In summary, our findings indicate for the first time that reduced levels, but not the absence, of gzmA could slightly ameliorate the disease progression in this animal model. info:eu-repo/grantAgreement/ES/AEI/PID2020-113963RB-I00 info:eu-repo/grantAgreement/ES/DGA/B29-20R info:eu-repo/grantAgreement/ES/ISCIII/FEDER/PI21-00372 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.6 2022 BIOCHEMISTRY & MOLECULAR BIOLOGY 66 / 285 = 0.232 2022 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 52 / 178 = 0.292 2022 Q2 T1 1.154 2022 Medicine (miscellaneous) 2022 Q1 Physical and Theoretical Chemistry 2022 Q1 Computer Science Applications 2022 Q1 Inorganic Chemistry 2022 Q1 Spectroscopy 2022 Q1 Organic Chemistry 2022 Q1 Molecular Biology 2022 Q2 Catalysis 2022 Q2 7.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Santiago, Llipsy de la Torre, Miriam Universidad de Zaragoza (orcid)0000-0002-7955-7164 Calvo, Ana Cristina Universidad de Zaragoza (orcid)0000-0001-5193-7782 Pardo, Julián Universidad de Zaragoza (orcid)0000-0003-0154-0730 Osta, Rosario Universidad de Zaragoza (orcid)0000-0001-5687-6704 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 1012 315 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Farmacología 23, 21 (2022), 13554 [15 pp.] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 3107747 http://zaguan.unizar.es/record/119999/files/texto_completo.pdf Versión publicada 2688978 http://zaguan.unizar.es/record/119999/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:119999 articulos driver 2024-03-18-12:34:12 ARTICLE