Seed-specific expression of truncated OsGAD2 produces GABA-enriched rice grains that influence a decrease in blood pressure in spontaneously hypertensive rats.
Gamma-aminobutyric acid (GABA) is a four-carbon amino acid that is commonly present in living organisms and functions as a major inhibitory neurotransmitter in mammals. It is understood to have a potentially anti-hypertensive effect in mammals. GABA is synthesized from glutamate by glutamate decarboxylase (GAD). In plants, GAD is regulated via its calmodulin-binding domain (CaMBD) by Ca(2+)/CaM. We have previously reported that a C-terminal truncated version of one of the five rice GAD isoforms, GAD2DeltaC, revealed higher enzymatic activity in vitro and that its over-expression resulted in exceptionally high GABA accumulation (Akama and Takaiwa, J Exp Bot 58:2699-2607, 2007). In this study, GAD2DeltaC, under the control of the rice glutelin promoter (GluB-1), was introduced into rice cells via Agrobacterium-mediated transformation to produce transgenic rice lines. Analysis of the free amino acid content of rice grains revealed up to about a 30-fold higher level of GABA than in non-transformed rice grains. There were also very high levels of various free protein amino acids in the seeds. GABA-enriched rice grains were milled to a fine powder for oral administration to spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). Six weeks of administration showed that transgenic rice brings about a 20 mmHg decrease in blood pressure in two different kinds of SHRs, while there was no significant hypotensive effect in WKYs. These results suggest an alternative way to control and/or cure hypertension in humans with GABA-enriched rice as part of a common daily diet.
Akama
Kazuhito
K
Department of Biological Science, Shimane University, Nishikawatsu 1060, Matsue, Shimane 690-8504, Japan. akama@life.shimane-u.ac.jp
Kanetou
Junko
J
Shimosaki
Shunsuke
S
Kawakami
Kouhei
K
Tsuchikura
Satoru
S
Takaiwa
Fumio
F
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D056625:Endosperm / Q000737:chemistry / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics*; D012275:Oryza / Q000235:genetics*; D030821:Plants, Genetically Modified / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014170:Transformation, Genetic; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000032:analysis
D000959:Antihypertensive Agents; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2