Record number :
2433597
Title of article :
Selective Inhibition of α-Galactosidase A with Antisense Oligodeoxynucleotide in Mesangial Cells: A Renal Cellular Model for Fabry Disease
Author/Authors :
Utsumi, Kouichi Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Itoh, Kohji Department of Medical Biotechnology - Institute for Medical Resources - Graduate School of Pharmaceutical Sciences - the University of Tokushima - Tokushima, Japan , Hirama, Akio Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Ueda, Kae Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Sakamaki, Masanori Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Kaneko, Tomohiro Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Yamazaki, Mineo Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Komaba, Yuichi Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Katsura, Ken-Ichiro Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Iino, Yasuhiko Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan , Katayama, Yasuo Department of Internal Medicine - Divisions of Neurology - Nephrology , and Rheumatology - Nippon Medical School - Tokyo, Japan
Pages :
4
From page :
397
To page :
400
Abstract :
Background and Aims: Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme α-galacotsidase (α-Gal) A. Accumulation of glycosphingolipids, especially globotriaosylceramide, leads to various organ damage in Fabry disease. Recently, replacement with recombinant α-Gal A has become available for the treatment of this disease. However, the pathogenic mechanism of this disease, which is the accumulation of glycosphingolipids, is still unknown. Understanding the pathogenesis of Fabry disease may allow more efficient treatments. We examined whether the selective inhibition of α-Gal A with phosphorothioate antisense oligonucleotides could be used as a renal cellular model for Fabry disease. Methods: Phosphorothioate antisense oligonucleotides designed to hyrbridize to sites on the human α-Gal A mRNA were tested for inhibition of α-Gal A expression in human mesangial cells. α-Gal A activity was measured using an artificial substrate, 4-methylumbelliferyl-α-D-galactoside. Results: Two antisense oligonucleotides selectively inhibited α-Gal A activity to below 20% of the mean control activity. These oligonucleotides did not affect other lysosomal enzyme activities. Conclusions: These data indicate that phosphorothioate oligonucleotides are capable of selectively inhibiting α-Gal A expression. It may be a useful model for renal mesangial cells in Fabry disease.
Keywords :
Fabry Disease , α-galactosidase A , Antisense Oligodeoxynucleotide , Globotriaosylceramide
Journal title :
Astroparticle Physics
Serial Year :
2010
Link To Document :
بازگشت