Biochemical characterization of vitreous and cardiac amyloid in Ile84Ser transthyretin amyloidosis

Juris J. Liepnieks, Donald L. Wilson, Merrill Benson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Plasma transthyretin (TTR) is synthesized in the liver and is the source for visceral amyloid deposits in TTR amyloidosis. However, TTR is also synthesized in the retinal pigment epithelium of the eye and choroid plexus of the brain. It has been postulated that vitreous amyloid, which is associated with approximately 20% of the known amyloidogenic TTR mutations, results from local synthesis of TTR in the eye. In order to elucidate if differences in amyloid between organs exists, we have analyzed vitreous and cardiac amyloid fibrils in Ile84Ser TTR patients for comparison. Analysis of guanidine hydrochloride solubilized protein from isolated vitreous and cardiac amyloid fibrils indicated that the amyloid TTR in both organs is highly proteolyzed with minor amounts of intact TTR present. While vitreous protein was amenable to direct Edman sequence analysis, cardiac protein gave low yields indicating it was mostly N-terminally blocked or inaccessible to Edman degradation. While vitreous contained major 11 kDa and minor 9 kDa fragments, cardiac contained at least three major fragments of 7-11 kDa. Vitreous protein was cleaved between Lys48-Thr49, while cardiac protein was cleaved at multiple sites in the residue 46-52 region. While deposits in both tissues were enriched in variant TTR, vitreous fibrils contained more variant protein than cardiac fibrils (80-89% vs. 60-65% Ser84TTR). These differences suggest that the mechanism or pathway of fibril formation may differ in various tissues.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalAmyloid
Volume13
Issue number3
DOIs
StatePublished - Sep 1 2006

Fingerprint

Prealbumin
Amyloid
Proteins
Pigment Epithelium of Eye
Choroid Plexus
Amyloidosis, Hereditary, Transthyretin-Related
Retinal Pigment Epithelium
Guanidine
Protein Sequence Analysis
Amyloid Plaques
Mutation
Liver
Brain

Keywords

  • Cardiac amyloid
  • Hereditary amyloidosis
  • Proteolysis
  • Transthyretin
  • Transthyretin fragments
  • Vitreous amyloid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Biochemical characterization of vitreous and cardiac amyloid in Ile84Ser transthyretin amyloidosis. / Liepnieks, Juris J.; Wilson, Donald L.; Benson, Merrill.

In: Amyloid, Vol. 13, No. 3, 01.09.2006, p. 170-177.

Research output: Contribution to journalArticle

Liepnieks, Juris J. ; Wilson, Donald L. ; Benson, Merrill. / Biochemical characterization of vitreous and cardiac amyloid in Ile84Ser transthyretin amyloidosis. In: Amyloid. 2006 ; Vol. 13, No. 3. pp. 170-177.
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