Proteasome Composition and Activity Changes in Cultured Fibroblasts Derived From Mucopolysaccharidoses Patients and Their Modulation by Genistein

Frontiers in Cell and Developmental Biology
Karolina PierzynowskaGrzegorz Węgrzyn

Abstract

In this study, we have asked whether proteasome composition and function are affected in cells derived from patients suffering from all types of mucopolysaccharidosis (MPS), an inherited metabolic disease caused by accumulation of undegraded glycosaminoglycans (GAGs). Moreover, we have tested if genistein, a small molecule proposed previously as a potential therapeutic agent in MPS, can modulate proteasomes, which might shed a new light on the molecular mechanisms of action of this isoflavone as a potential drug for macromolecule storage diseases. Significant changes in expression of various proteasome-linked genes have been detected during transcriptomic (RNA-seq) analyses in vast majority of MPS types. These results were corroborated by demonstration of increased proteasomal activities in MPS cells. However, GAGs were not able to stimulate the 26S proteasome in vitro, suggesting that the observed activation in cells is indirect rather than arising from direct GAG-proteasome interactions. Genistein significantly reduced proteasomal activities in fibroblasts derived from patients suffering from all MPS types, while its effects on in vitro 26S proteasome activity were negligible. Unexpectedly, levels of many proteasomal subunits...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Lidia GaffkeGrzegorz Węgrzyn
May 1, 2021·International Journal of Molecular Sciences·Graciela ArgüelloSilvana Zanlungo

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Datasets Mentioned

BETA
GM03722
PRJNA562649

Methods Mentioned

BETA
Chips
RNA-seq
Profiler
PCR
ubiquitination

Software Mentioned

Cuffmerge
BioMart
Ensembl
Cuffquant
QuickGO
Proteome Profiler
R

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