Seed-specific expression of truncated OsGAD2 produces GABA-enriched rice grains that influence a decrease in blood pressure in spontaneously hypertensive rats |
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Authors: | Kazuhito Akama Junko Kanetou Shunsuke Shimosaki Kouhei Kawakami Satoru Tsuchikura Fumio Takaiwa |
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Institution: | (1) Department of Biological Science, Shimane University, Nishikawatsu 1060, Matsue Shimane, 690-8504, Japan;(2) Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo Shimane, 693-8501, Japan;(3) Disease Model Cooperative Research Association, Hamamatsu Shizuoka, 433-8114, Japan;(4) Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, Kannondai 2-1-2, Tsukuba Ibaraki, 305-8602, Japan |
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Abstract: | 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 Ca2+/CaM. We have previously reported that a C-terminal truncated version of one of the five rice GAD isoforms, GAD2ΔC, 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, GAD2ΔC, 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. |
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