Proteasome inhibitors improve the function of mutant lysosomal α-glucosidase in fibroblasts from Pompe disease patient carrying c.546G&gt;T mutation

Shimada, Yohta; Nishida, Hikaru; Nishiyama, Yurika; Kobayashi, Hiroshi; Higuchi, Takashi; Eto, Yoshikatsu; Ida, Hiroyuki; Ohashi, Toya

doi:10.1016/j.bbrc.2011.10.038

Cited by 18 publications

(20 citation statements)

References 22 publications

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“…We previously showed that bortezomib rescues the function of GAA in fibroblasts from a patient with Pompe disease carrying the c.546G>T mutation (Shimada et al 2011). However, the responsiveness of almost all GAA mutations to bortezomib has not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Immunofluorescence staining against both GAA and LAMP2 was performed according to a procedure previously described (Shimada et al 2011). Fibroblasts were incubated with the primary antibodies and visualized by using Alexa 488-conjugated anti-rabbit IgG and Alexa 594-conjugated anti-mouse IgG secondary antibodies (Invitrogen, Carlsbad, CA) followed by counterstaining with DAPI (Vector Laboratories).…”

Section: Immunocytochemistrymentioning

confidence: 99%

“…Protein samples for Western blot were prepared as previously described (Shimada et al 2011). Briefly, fibroblasts were extracted with 50 mM Tris-HCl, pH 7.5 containing 2% SDS, and PIC.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…GAA activities in fibroblasts and HEK293T cells were assayed using 4-methylumbelliferyl a-D-glucopyranoside as previously described (Shimada et al 2011).…”

Section: Quantitative Analyses Of Proteins and Gaa Activitymentioning

confidence: 99%

“…In Pompe disease, imino sugars such as deoxynojirimycin (DNJ) and N-butyl-DNJ (NB-DNJ) have shown to improve the function of several mutant GAAs (Okumiya et al 2007;Parenti et al 2007;Flanagan et al 2009). We previously reported that the proteasome inhibitor bortezomib as well as imino sugars can exert a positive effect on mutant GAA in fibroblasts from a patient with Pompe disease carrying the c.546G>T mutation (Shimada et al 2011). In addition, bortezomib, which is a therapeutic drug for multiple myeloma, has recently shown to be a safe treatment to induce the effective reduction of anti-rhGAA antibody titers in patients with infantile Pompe disease who received ERT (Banugaria et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Proteasome Inhibitor Bortezomib Enhances the Activity of Multiple Mutant Forms of Lysosomal α-Glucosidase in Pompe Disease

et al. 2014

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Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid aglucosidase (GAA). Recently, we showed that function of mutant GAA in fibroblasts derived from Pompe disease patient carrying c.546G>T mutation is improved by treatment with proteasome inhibitor bortezomib as well as pharmacological chaperone (PC). However, bortezomib-responsive GAA mutations are not fully characterized. In this study, we showed the effect of bortezomib on different mutants of GAA in patient fibroblasts and transiently expressed HEK293T cells. Bortezomib increased the maturation and residual activity of GAA in patient fibroblasts carrying PC-responsive M519V and PC-unresponsive C647W mutations. Enhanced colocalization of GAA with lysosomal marker LAMP2 was also observed in patient fibroblasts after treatment with bortezomib. When four distinct mutant GAAs, which show different response to PC, were overexpressed in HEK293T cells, bortezomib improved the activity of M519V, S529V, and C647W in them (1.3-5.9-fold). These results indicate that bortezomib enhances the activity of some PC-unresponsive GAA mutants as well as PC-responsive mutants.

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Section: Discussionmentioning

confidence: 99%

Section: Immunocytochemistrymentioning

confidence: 99%

“…Protein samples for Western blot were prepared as previously described (Shimada et al 2011). Briefly, fibroblasts were extracted with 50 mM Tris-HCl, pH 7.5 containing 2% SDS, and PIC.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…GAA activities in fibroblasts and HEK293T cells were assayed using 4-methylumbelliferyl a-D-glucopyranoside as previously described (Shimada et al 2011).…”

Section: Quantitative Analyses Of Proteins and Gaa Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proteasome Inhibitor Bortezomib Enhances the Activity of Multiple Mutant Forms of Lysosomal α-Glucosidase in Pompe Disease

et al. 2014

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High-Throughput Screen Fails to Identify Compounds That Enhance Residual Enzyme Activity of Mutant N-Acetyl-α-Glucosaminidase in Mucopolysaccharidosis Type IIIB

et al. 2017

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Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats

et al. 2014

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We previously showed that mesenchymal stem cells (MSCs) can differentiate into a functional miniature kidney, suggesting that MSCs may be a cell source for kidney regeneration. However, MSCs from long-term dialysis patients, which have been exposed to uremic toxin, can exhibit reduced viability. Therefore, the aim of this study was to examine the gene expression profiles and differentiation capabilities of bone marrow- and adipose-derived MSCs from chronic kidney disease (CKD) model rats. CKD was induced in rats by adenine feeding, and then MSCs were isolated from bone marrow (BMSCs) and adipose tissue (ASCs). After confirming MSC surface marker expression, comprehensive gene expression profiles were obtained by RT-PCR array. MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, and histological and/or functional assays were performed. Tgfb3 expression was up-regulated, while Bmp6, Gdf15, Mmp2, and Vegfa were down-regulated in CKD-ASCs compared with Control-ASCs. There were no significant differences in the gene expression of stemness markers, and the morphology of cells that underwent adipogenesis, osteogenesis, and chondrogenesis, or GPDH activity between CKD and control groups. Comparing BMSCs with ASCs, gene expression of Bglap, Bmp4, Igf1, Itgax, Pparg, Ptprc, and Tnf were up-regulated, while Col1a1, Mmp2, Sox9, and Vegfa were down-regulated in both CKD and control groups. Uremic toxin in CKD rats had a small effect on the gene expression and differentiation of MSCs. However, long-term exposure to uremic toxin and the differences in gene expression of MSCs derived from bone marrow or adipose tissue may affect renal regeneration.

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Proteasome inhibitors improve the function of mutant lysosomal α-glucosidase in fibroblasts from Pompe disease patient carrying c.546G>T mutation

Cited by 18 publications

References 22 publications

Proteasome Inhibitor Bortezomib Enhances the Activity of Multiple Mutant Forms of Lysosomal α-Glucosidase in Pompe Disease

Proteasome Inhibitor Bortezomib Enhances the Activity of Multiple Mutant Forms of Lysosomal α-Glucosidase in Pompe Disease

High-Throughput Screen Fails to Identify Compounds That Enhance Residual Enzyme Activity of Mutant N-Acetyl-α-Glucosaminidase in Mucopolysaccharidosis Type IIIB

Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats

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