PMID: 9434098Jan 20, 1998Paper

Down regulation of a harmful variant protein by replacement of its normal protein

Biochimica Et Biophysica Acta
Y AndoM Ando

Abstract

To compensate for the hypoprotein and hypoalbuminemia of familial amyloidotic polyneuropathy (FAP) patients, 800 ml of fresh frozen plasma (FFP) was intravenously administered and change in total and variant transthyretin (TTR) levels were measured in the plasma. After injection of FFP, total plasma TTR levels were elevated and variant TTR levels decreased from 24 to 48 h, accompanied by an elevation of plasma total protein, albumin levels and TTR levels. To elucidate the mechanism of this phenomenon, a large amount of purified normal TTR from normal human plasma was intravenously injected in mice and FAP patients. By intravenous injection of 3 mg of the purified TTR to C57Black6, the expression of TTR mRNA decreased from 6 to 24 h post injection, and gradually increased up to 48 h post injection. After injecting 400 mg of normal TTR in each of 3 FAP patients, total plasma TTR levels were elevated and variant TTR levels decreased significantly from 24 to 48 h. These results suggested that down regulation of the harmful protein by replacement of its normal form of the protein occurred by this method. This phenomenon should be applied as the basis for one of the useful methods for decreasing the harmful proteins in the circulation.

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Citations

Nov 1, 2003·Biochemical and Biophysical Research Communications·Xuguo SunHiroaki Okabe
Jun 25, 2002·Journal of Molecular Biology·Tara Nath NiraulaKazuyuki Akasaka
Oct 18, 2005·Biochemical and Biophysical Research Communications·Takayuki KurosawaOsamu Onodera
May 4, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Tomoe KugimiyaYukio Ando
Feb 13, 2004·Gene Therapy·M NakamuraK Yamamura
Dec 10, 2008·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Yohei MisumiYukio Ando

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