title: Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis.
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.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 226-8501 Yokohama, Japan.
authors.forename: Chikanori
authors.initials: C
authors.lastname: Kuramori
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Hase
authors.forename: Koichi
authors.initials: K
authors.lastname: Hoshikawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Nishi
authors.forename: Takako
authors.initials: T
authors.lastname: Hishiki
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nashimoto
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hajime
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Kataoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D006004:Glycogen Debranching Enzyme System / Q000378:metabolism*; D050261:Glycogenolysis / Q000187:drug effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006004:Glycogen Debranching Enzyme System; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate