Organic acids metabolism and GABA shunt involved in maintaining quality of Malus domestica by methyl jasmonate treatment.

Apples (cv. Golden Delicious) were used as the materials to investigate methyl jasmonate (MeJA) dipping on quality parameters, organic acids metabolism and GABA shunt during storage at 21 ± 1 °C and 75 ± 5 % relative humidity. Results demonstrated that MeJA treatment reduced mass loss, respiratory intensity and ethylene release, and maintained higher flesh firmness and soluble solid content of apples. MeJA also decreased malic acid content, increased succinic and tartaric acids contents, and inhibited cytoplasmic aconitase (Cyt-ACO), NADP-malate (NADP-ME), phosphoenolpyruvate dehydrogenase (PEPC), mitochondrial citrate synthase (Mit-CS), glutamate dehydrogenase (GAD), and GABA transferase (GABA-T) activities in apples. NADP-isocitrate dehydrogenase (NADP-IDH), mitochondrial cis-aconitase (Mit-ACO), and cytoplasmic NAD-malate dehydrogenase (CytNAD-MDH) activities in apples were also enhanced by MeJA dipping. Moreover, MeJA dipping enhanced MdCytNAD-MDH and MdNADP-IDH expressions, and down-regulated MdGAD, MdGABA-T, MdNADP-ME, MdPEPC, MdCyt-ACO and MdMit-CS expressions in apples. These results suggest that MeJA dipping can maintain storage quality of "Golden Delicious" apples by regulating organic acids metabolism and GABA shunt.

A new drug design targeting the adenosinergic system for Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease caused by a CAG trinucleotide expansion in the Huntingtin (Htt) gene. The expanded CAG repeats are translated into polyglutamine (polyQ), causing aberrant functions as well as aggregate formation of mutant Htt. Effective treatments for HD are yet to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a novel dual-function compound, N(6)-(4-hydroxybenzyl)adenine riboside (designated T1-11) which activates the A(2A)R and a major adenosine transporter (ENT1). T1-11 was originally isolated from a Chinese medicinal herb. Molecular modeling analyses showed that T1-11 binds to the adenosine pockets of the A(2A)R and ENT1. Introduction of T1-11 into the striatum significantly enhanced the level of striatal adenosine as determined by a microdialysis technique, demonstrating that T1-11 inhibited adenosine uptake in vivo. A single intraperitoneal injection of T1-11 in wildtype mice, but not in A(2A)R knockout mice, increased cAMP level in the brain. Thus, T1-11 enters the brain and elevates cAMP via activation of the A(2A)R in vivo. Most importantly, addition of T1-11 (0.05 mg/ml) to the drinking water of a transgenic mouse model of HD (R6/2) ameliorated the progressive deterioration in motor coordination, reduced the formation of striatal Htt aggregates, elevated proteasome activity, and increased the level of an important neurotrophic factor (brain derived neurotrophic factor) in the brain. These results demonstrate the therapeutic potential of T1-11 for treating HD. CONCLUSIONS/SIGNIFICANCE: The dual functions of T1-11 enable T1-11 to effectively activate the adenosinergic system and subsequently delay the progression of HD. This is a novel therapeutic strategy for HD. Similar dual-function drugs aimed at a particular neurotransmitter system as proposed herein may be applicable to other neurotransmitter systems (e.g., the dopamine receptor/dopamine transporter and the serotonin receptor/serotonin transporter) and may facilitate the development of new drugs for other neurodegenerative diseases.