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7 results on '"Gb3 synthase"'

1. Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease.

Author

Beraza-Millor, Marina, Rodríguez-Castejón, Julen, Miranda, Jonatan, del Pozo-Rodríguez, Ana, Rodríguez-Gascón, Alicia, and Solinís, María Ángeles

Subjects
*ANGIOKERATOMA corporis diffusum, *RNA, *GOLD nanoparticles, *NANOPARTICLES, *GENE therapy
Abstract

Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT. [ABSTRACT FROM AUTHOR]

Published
2023
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2. Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease

Author

Marina Beraza-Millor, Julen Rodríguez-Castejón, Jonatan Miranda, Ana del Pozo-Rodríguez, Alicia Rodríguez-Gascón, and María Ángeles Solinís

Subjects
substrate reduction therapy, solid lipid nanoparticles, siRNA, Fabry disease, Gb3 synthase, gold nanoparticles, Pharmacy and materia medica, RS1-441
Abstract

Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT.

Published
2023
Full Text
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3. Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease

Author

Farmacia y ciencias de los alimentos, Farmazia eta elikagaien zientziak, Beraza Millor, Marina, Rodríguez Castejón, Julen, Miranda Gómez, Jonatan, Del Pozo Rodríguez, Ana, Rodríguez Gascón, Alicia, Solinís Aspiazu, María Ángeles, Farmacia y ciencias de los alimentos, Farmazia eta elikagaien zientziak, Beraza Millor, Marina, Rodríguez Castejón, Julen, Miranda Gómez, Jonatan, Del Pozo Rodríguez, Ana, Rodríguez Gascón, Alicia, and Solinís Aspiazu, María Ángeles

Abstract

Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT.

Published
2023

4. Lose the lipid: renoprotection conferred by Gb3 synthase knockout

Author

Ora A. Weisz and Anatalia Labilloy

Subjects
0301 basic medicine, Endocytic cycle, 030232 urology & nephrology, Globotriaosylceramide, Renal function, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Albumins, medicine, Cytotoxic T cell, Animals, Gb3 synthase, chemistry.chemical_classification, ATP synthase, biology, Chemistry, Trihexosylceramides, Acute kidney injury, Acute Kidney Injury, medicine.disease, Galactosyltransferases, Cell biology, 030104 developmental biology, Enzyme, Nephrology, biology.protein
Abstract

The ability of proximal tubule cells to internalize filtered proteins over a broad concentration range is essential for maintaining a protein-free urine but also renders these cells uniquely susceptible to cytotoxic damage. Morace et al. find that knockout of globotriaosylceramide synthase, an enzyme required for production of Gb3 and other members of the globo series of glycosphingolipids, impairs endocytic uptake of filtered proteins and preserves kidney function in mouse models of acute kidney injury.

Published
2019

5. Increased globotriaosylceramide levels in a transgenic mouse expressing human 1,4-galactosyltransferase and a mouse model for treating Fabry disease

Author

Hidekatsu Yoshioka, Koichi Furukawa, Chikara Shiozuka, Ryoji Hamanaka, Kozue Uchio-Yamada, Satoshi Ishii, Kazuaki Mannen, Takanori Kunieda, Junichiro Matsuda, Shinji Yano, Ashok B. Kulkarni, Atsumi Taguchi, Yoko Noguchi, and Shigeo Yokoyama

Subjects
Genetically modified mouse, 1-Deoxynojirimycin, Mutant, Globotriaosylceramide, Mice, Transgenic, Biology, Kidney, Biochemistry, Mice, chemistry.chemical_compound, medicine, Animals, Humans, Gb3 synthase, Molecular Biology, Crosses, Genetic, Mice, Knockout, Galactosyltransferase, Trihexosylceramides, Regular Papers, General Medicine, Galactosyltransferases, medicine.disease, Molecular biology, Fabry disease, Up-Regulation, Enzyme Activation, Disease Models, Animal, Liver, chemistry, alpha-Galactosidase, Fabry Disease, Female, Spleen, Molecular Chaperones
Abstract

Fabry disease is a lysosomal storage disorder caused by an α-galactosidase A (α-Gal A) deficiency and resulting in the accumulation of glycosphingolipids, predominantly globotriaosylceramide (Gb3). A transgenic mouse expressing the human α-Gal A R301Q mutant in an α-Gal A-knockout background (TgM/KO) should be useful for studying active-site-specific chaperone (ASSC) therapy for Fabry disease. However, the Gb3 content in the heart tissue of this mouse was too low to detect an ASSC-induced effect. To increase the Gb3 levels in mouse organs, we created transgenic mice (TgG3S) expressing human α1,4-galactosyltransferase (Gb3 synthase). High levels of Gb3 were observed in all major organs of the TgG3S mouse. A TgG3S (+/−)M(+/−)/KO mouse was prepared by cross-breeding the TgG3S and TgM/KO mice and the Gb3 content in the heart of the TgG3S(+/−)M(+/−)/KO mouse was 1.4 µg/mg protein, higher than in the TgM(+/−)/KO (

Published
2010

6. Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression

Author

Jong-Seo Shin, In-Sun Shin, Kyong-Il Sung, Hyun-Yong Jang, Satoshi Ishii, Byong-Wan Kim, and Byung-Sung Park

Subjects
Globosides, biology, Trihexosylceramides, Globotriaosylceramide, Shiga toxin, General Medicine, Galactosyltransferases, biology.organism_classification, Biochemistry, Molecular biology, Shiga Toxin, HeLa, chemistry.chemical_compound, Glycolipid, chemistry, Cell Clone, biology.protein, Humans, Gb3 synthase, Cytotoxicity, Receptor, Molecular Biology, HeLa Cells
Abstract

Globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4) are the proposed functional receptors for Shiga toxin (Stx). To elucidate the effect of Gb3 content on Stx-induced cytotoxicity in HeLa cells, we cloned HeLa cells and determined the correlation between glycolipids content and Stx-induced cytotoxicity. The 29 HeLa cell clone (HLCC) lines used showed a wide range of sensitivity to Stx, compared to Gb3-rich cells which were more sensitive, showing as little as 20% viability to 100 pg/ml Stx. In contrast, Gb3-deficient cells proved resistant as they were more than 80% viable to 100 ng/ml Stx. Gb3 content in the HLCC lines corresponded with Stxs-induced cytotoxicity as well as Gb3 synthase expression, but no correlation with Gb4 content was noted. These data show that Gb3 content, which is regulated by the expression of Gb3 synthase, determines the sensitivity of HeLa cells toward Stx.

Published
2009

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