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The C‐terminal Domain of Selenoprotein P Is Needed for Maintenance of Selenium Homeostasis
Author(s) -
Motley Amy K,
Hill Kristina E,
Zhou Jiadong,
Austin Lori M,
Olson Gary E,
Atkins John F,
Gesteland Raymond F,
Burk Raymond F
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1067-b
Subject(s) - selenium , selenoprotein , homeostasis , selenoprotein p , selenocysteine , amino acid , chemistry , serine , medicine , endocrinology , biology , biochemistry , enzyme , cysteine , glutathione , glutathione peroxidase , organic chemistry
Selenoprotein P (Se‐P) is a selenium‐rich plasma protein important in selenium (Se) homeostasis. It has two domains with respect to Se. Its N‐terminal domain (amino acid residues 1–238) contains one selenocysteine (Sec) and has been postulated to have enzymatic activity. Its C‐terminal domain (amino acid residues 239–361) contains 9 Sec and has been postulated to function in delivery of Se to tissues. Deletion of Se‐P (Se‐P KO) disrupts Se homeostasis, leading to decreased whole‐body Se and dysfunction of several tissues. We have produced a mouse expressing a truncated form of Se‐P (Se‐P(t)). The expressed protein contains the N‐terminal domain but not the C‐terminal domain. Mass spec analysis of purified Se‐P(t) shows that the protein terminates after the serine‐238 that precedes the second Sec. Thus, Se‐P(t) is the N‐terminal domain of Se‐P. Se‐P(t) mice fed a Se‐deficient diet did not have the shortened stride displayed by Se‐P KO mice, but, when fed a low‐Se diet, they displayed episodes of hyperactivity and died in a manner similar to Se‐P KO mice. Se supplementation prevented the hyperactive episodes and death. Tissue Se levels in Se‐P(t) mice were similar to those in Se‐P KO mice. Male Se‐P(t) mice were infertile and had abnormal spermatozoa that appeared similar to those in Se‐P KO mice. These results are consistent with the C‐terminal domain of Se‐P being important in Se transport and homeostasis. Supported by NIH ES02497.