Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy

Kazuaki Taguchi, Hirofumi Jono, Tomoe Kugimiya-Taguchi, Saori Nagao, Yu Su, Keishi Yamasaki, Mineyuki Mizuguchi, Toru Maruyama, Yukio Ando, Masaki Otagiri

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo. Main methods: For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant amyloidogenic TTR Val30Met (rATTR V30M) were labeled with iodine and administered to Sprague-Dawley rats and analbuminemia rats (NAR: Nagase Analbuminemia Rats). The deposition of ATTR V30M was also analyzed by immunohistochemistry in the transgenic (Tg) rats possessing a human ATTR V30M gene (ATTR V30M Tg rats) and NAR possessing a human ATTR V30M gene (ATTR V30M Tg NAR). Key findings: The presence of albumin had no effect on the tissue distribution of either rTTR or rATTR V30M. However, more ATTR V30M was deposited in the hearts, stomachs and small intestines of ATTR V30M Tg NAR rats, compared to ATTR V30M Tg rats. Significance: Although the disposition of TTR and ATTR V30M was unaffected by the presence of albumin, the deposition of ATTR V30M in some organs was apparently increased in the absence of albumin compared to the presence of albumin. These results show that albumin would contribute to suppressing the tissue deposition of TTR in pathogenesis of FAP, but does not affect the disposition of TTR.

Original languageEnglish
Pages (from-to)1017-1022
Number of pages6
JournalLife Sciences
Volume93
Issue number25-26
DOIs
Publication statusPublished - 2013 Dec 18
Externally publishedYes

Fingerprint

Prealbumin
Polyneuropathies
Albumins
Rats
Tissue
Transgenic Rats
Amyloid
Genes
Acetylglucosaminidase
Pharmacokinetics
Tissue Distribution
Iodine
Small Intestine
Sprague Dawley Rats
Stomach
Immunohistochemistry

Keywords

  • Albumin
  • Familial amyloidotic polyneuropathy
  • Transthyretin

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy. / Taguchi, Kazuaki; Jono, Hirofumi; Kugimiya-Taguchi, Tomoe; Nagao, Saori; Su, Yu; Yamasaki, Keishi; Mizuguchi, Mineyuki; Maruyama, Toru; Ando, Yukio; Otagiri, Masaki.

In: Life Sciences, Vol. 93, No. 25-26, 18.12.2013, p. 1017-1022.

Research output: Contribution to journalArticle

Taguchi, K, Jono, H, Kugimiya-Taguchi, T, Nagao, S, Su, Y, Yamasaki, K, Mizuguchi, M, Maruyama, T, Ando, Y & Otagiri, M 2013, 'Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy', Life Sciences, vol. 93, no. 25-26, pp. 1017-1022. https://doi.org/10.1016/j.lfs.2013.10.031
Taguchi, Kazuaki ; Jono, Hirofumi ; Kugimiya-Taguchi, Tomoe ; Nagao, Saori ; Su, Yu ; Yamasaki, Keishi ; Mizuguchi, Mineyuki ; Maruyama, Toru ; Ando, Yukio ; Otagiri, Masaki. / Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy. In: Life Sciences. 2013 ; Vol. 93, No. 25-26. pp. 1017-1022.
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abstract = "Aims: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo. Main methods: For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant amyloidogenic TTR Val30Met (rATTR V30M) were labeled with iodine and administered to Sprague-Dawley rats and analbuminemia rats (NAR: Nagase Analbuminemia Rats). The deposition of ATTR V30M was also analyzed by immunohistochemistry in the transgenic (Tg) rats possessing a human ATTR V30M gene (ATTR V30M Tg rats) and NAR possessing a human ATTR V30M gene (ATTR V30M Tg NAR). Key findings: The presence of albumin had no effect on the tissue distribution of either rTTR or rATTR V30M. However, more ATTR V30M was deposited in the hearts, stomachs and small intestines of ATTR V30M Tg NAR rats, compared to ATTR V30M Tg rats. Significance: Although the disposition of TTR and ATTR V30M was unaffected by the presence of albumin, the deposition of ATTR V30M in some organs was apparently increased in the absence of albumin compared to the presence of albumin. These results show that albumin would contribute to suppressing the tissue deposition of TTR in pathogenesis of FAP, but does not affect the disposition of TTR.",
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T1 - Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy

AU - Taguchi, Kazuaki

AU - Jono, Hirofumi

AU - Kugimiya-Taguchi, Tomoe

AU - Nagao, Saori

AU - Su, Yu

AU - Yamasaki, Keishi

AU - Mizuguchi, Mineyuki

AU - Maruyama, Toru

AU - Ando, Yukio

AU - Otagiri, Masaki

PY - 2013/12/18

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N2 - Aims: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo. Main methods: For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant amyloidogenic TTR Val30Met (rATTR V30M) were labeled with iodine and administered to Sprague-Dawley rats and analbuminemia rats (NAR: Nagase Analbuminemia Rats). The deposition of ATTR V30M was also analyzed by immunohistochemistry in the transgenic (Tg) rats possessing a human ATTR V30M gene (ATTR V30M Tg rats) and NAR possessing a human ATTR V30M gene (ATTR V30M Tg NAR). Key findings: The presence of albumin had no effect on the tissue distribution of either rTTR or rATTR V30M. However, more ATTR V30M was deposited in the hearts, stomachs and small intestines of ATTR V30M Tg NAR rats, compared to ATTR V30M Tg rats. Significance: Although the disposition of TTR and ATTR V30M was unaffected by the presence of albumin, the deposition of ATTR V30M in some organs was apparently increased in the absence of albumin compared to the presence of albumin. These results show that albumin would contribute to suppressing the tissue deposition of TTR in pathogenesis of FAP, but does not affect the disposition of TTR.

AB - Aims: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo. Main methods: For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant amyloidogenic TTR Val30Met (rATTR V30M) were labeled with iodine and administered to Sprague-Dawley rats and analbuminemia rats (NAR: Nagase Analbuminemia Rats). The deposition of ATTR V30M was also analyzed by immunohistochemistry in the transgenic (Tg) rats possessing a human ATTR V30M gene (ATTR V30M Tg rats) and NAR possessing a human ATTR V30M gene (ATTR V30M Tg NAR). Key findings: The presence of albumin had no effect on the tissue distribution of either rTTR or rATTR V30M. However, more ATTR V30M was deposited in the hearts, stomachs and small intestines of ATTR V30M Tg NAR rats, compared to ATTR V30M Tg rats. Significance: Although the disposition of TTR and ATTR V30M was unaffected by the presence of albumin, the deposition of ATTR V30M in some organs was apparently increased in the absence of albumin compared to the presence of albumin. These results show that albumin would contribute to suppressing the tissue deposition of TTR in pathogenesis of FAP, but does not affect the disposition of TTR.

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KW - Familial amyloidotic polyneuropathy

KW - Transthyretin

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