Anti-hypertensive activity of genetically modified soybean seeds accumulating novokinin.
Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), which has been designed based on the structure of ovokinin (2-7), significantly reduces the systolic blood pressure at a dose of 100 microg/kg after oral administration in spontaneously hypertensive rats (SHRs). In this study, we generated a transgenic soybean which accumulates novokinin. A vector encoding a modified beta-conglycinin alpha' subunit (4novokinin-alpha') in which four novokinin sequences have been incorporated by site-directed mutagenesis was introduced into somatic embryos by whisker-mediated gene transformation to produce a transgenic soybean. The 4novokinin-alpha' occupied 0.5% of total soluble protein and 5% of the beta-conglycinin alpha' subunit in the transgenic soybean seeds. Protein extracted from the transgenic soybean reduced systolic blood pressure after single oral administration in SHRs at a dose of 0.15 g/kg. Defatted flour from the transgenic soybean also reduced the systolic blood pressure at a dose of 0.25 g/kg. Thus, the 4novokinin-alpha' produced in soybean exhibited an anti-hypertensive activity in SHRs after oral administration.
Yamada
Yuko
Y
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan. yyamada@kais.kyoto-u.ac.jp
Nishizawa
Keito
K
Yokoo
Megumi
M
Zhao
Hui
H
Onishi
Kunihiko
K
Teraishi
Masayoshi
M
Utsumi
Shigeru
S
Ishimoto
Masao
M
Yoshikawa
Masaaki
M
D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015139:Blotting, Southern; D015151:Immunoblotting; D008297:Male; D009842:Oligopeptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D012639:Seeds / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D030262:Soybean Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D013025:Glycine max / Q000235:genetics / Q000378:metabolism*
D000959:Antihypertensive Agents; C511871:Arg-Pro-Leu-Lys-Pro-Trp; D009842:Oligopeptides; D030262:Soybean Proteins