Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis

Chikanori Kuramori, Yasuyoshi Hase, Koichi Hoshikawa, Keiko Watanabe, Takeyuki Nishi, Takako Hishiki, Tomoyoshi Soga, Akihiro Nashimoto, Yasuaki Kabe, Yuki Yamaguchi, Hajime Watanabe, Kohsuke Kataoka, Makoto Suematsu, Hiroshi Handa

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Phthalate esters are commonly used plasticizers; however, some are suspected to cause reproductive toxicity. Administration of high doses of di-(2-ethylhexyl) phthalate (DEHP) induces germ cell death in male rodents. Mono-(2-ethylhexyl) phthalate (MEHP), a hydrolyzed metabolite of DEHP, appears to be responsible for this testicular toxicity; however, the underlying mechanism of this chemical's action remains unknown. Here, using a one-step affinity purification procedure, we identified glycogen debranching enzyme (GDE) as a phthalate-binding protein. GDE has oligo-1,4-1,4-glucanotransferase and amylo-1,6-glucosidase activities, which are responsible for the complete degradation of glycogen to glucose. Our findings demonstrate that MEHP inhibits the activity of oligo-1,4-1,4-glucanotransferase, but not of amylo-1,6-glucosidase. Among various phthalate esters tested, MEHP specifically binds to and inhibits GDE. We also show that DEHP administration affects glycogen metabolism in rat testis. Thus, inhibition of GDE by MEHP may play a role in germ cell apoptosis in the testis.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalToxicological Sciences
Volume109
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

Glycogen Debranching Enzyme System
Glycogen
Metabolism
Testis
Rats
amylo-1,6-glucosidase
Germ Cells
Toxicity
Esters
Pharmacologic Actions
Enzyme inhibition
Plasticizers
Cell death
Metabolites
Purification
mono-(2-ethylhexyl)phthalate
phthalic acid
Rodentia
Carrier Proteins
Cell Death

Keywords

  • Germ cell
  • Glycogen debranching enzyme
  • Glycogen metabolism
  • Metabolome analysis
  • Phthalate esters

ASJC Scopus subject areas

  • Toxicology

Cite this

Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis. / Kuramori, Chikanori; Hase, Yasuyoshi; Hoshikawa, Koichi; Watanabe, Keiko; Nishi, Takeyuki; Hishiki, Takako; Soga, Tomoyoshi; Nashimoto, Akihiro; Kabe, Yasuaki; Yamaguchi, Yuki; Watanabe, Hajime; Kataoka, Kohsuke; Suematsu, Makoto; Handa, Hiroshi.

In: Toxicological Sciences, Vol. 109, No. 1, 2009, p. 143-151.

Research output: Contribution to journalArticle

Kuramori, C, Hase, Y, Hoshikawa, K, Watanabe, K, Nishi, T, Hishiki, T, Soga, T, Nashimoto, A, Kabe, Y, Yamaguchi, Y, Watanabe, H, Kataoka, K, Suematsu, M & Handa, H 2009, 'Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis', Toxicological Sciences, vol. 109, no. 1, pp. 143-151. https://doi.org/10.1093/toxsci/kfp041
Kuramori, Chikanori ; Hase, Yasuyoshi ; Hoshikawa, Koichi ; Watanabe, Keiko ; Nishi, Takeyuki ; Hishiki, Takako ; Soga, Tomoyoshi ; Nashimoto, Akihiro ; Kabe, Yasuaki ; Yamaguchi, Yuki ; Watanabe, Hajime ; Kataoka, Kohsuke ; Suematsu, Makoto ; Handa, Hiroshi. / Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis. In: Toxicological Sciences. 2009 ; Vol. 109, No. 1. pp. 143-151.
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