Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis.
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.
Kuramori
Chikanori
C
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 226-8501 Yokohama, Japan.
Hase
Yasuyoshi
Y
Hoshikawa
Koichi
K
Watanabe
Keiko
K
Nishi
Takeyuki
T
Hishiki
Takako
T
Soga
Tomoyoshi
T
Nashimoto
Akihiro
A
Kabe
Yasuaki
Y
Yamaguchi
Yuki
Y
Watanabe
Hajime
H
Kataoka
Kohsuke
K
Suematsu
Makoto
M
Handa
Hiroshi
H
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
D006004:Glycogen Debranching Enzyme System; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate