title: The hypocholesterolemic activity of transgenic rice seed accumulating lactostatin, a bioactive peptide derived from bovine milk β-lactoglobulin.
abstract: Lactostatin is a novel pentapeptide (IIAEK) derived from bovine milk β-lactoglobulin with greater hypocholesterolemic activity than β-sitosterol, the drug commonly used to treat hypercholesterolemia. We developed transgenic rice expressing lactostatin as a fusion protein with seed storage protein (SSP) glutelins under the control of three different endosperm-specific promoters. Lactostatin accumulated in transgenic rice seed at approximately 1.6 mg/g seeds (dry seeds) without any apparent influence on seed traits such as endogenous SSP expression levels or alterations in the intracellular structures of endosperm cells. Short-term (three day) oral administration of the glutelin fraction containing lactostatin (namely three times of 300 mg/kg body weight/day) extracted from transgenic rice seeds resulted in hypocholesterolemic activity in rats; namely, the serum low-density-lipoprotein (LDL) cholesterol level was significantly reduced accompanied by a significant increase in beneficial serum high-density-lipoprotein (HDL) cholesterol.
authors.affiliation: Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan.
authors.forename: Yuhya
authors.initials: Y
authors.lastname: Wakasa
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tamakoshi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ohno
authors.forename: Sakiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagaoka
authors.forename: Fumio
authors.initials: F
authors.lastname: Takaiwa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology*; D015139:Blotting, Southern; D002417:Cattle; D007782:Lactoglobulins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008892:Milk / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D012275:Oryza / Q000196:embryology*; D030821:Plants, Genetically Modified / Q000196:embryology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D007782:Lactoglobulins; D009842:Oligopeptides; C516979:lactostatin