SummaryArsenic (As) contamination in a paddy environment can cause phytotoxicity and elevated As accumulation in rice (Oryza sativa). The mechanism of As detoxification in rice is still poorly understood.We isolated an arsenate (As(V))-sensitive mutant of rice. Genomic resequencing and complementation identified OsCLT1, encoding a CRT-like transporter, as the causal gene for the mutant phenotype.OsCLT1 is localized to the envelope membrane of plastids. The glutathione and cglutamylcysteine contents in roots of Osclt1 and RNA interference lines were decreased markedly compared with the wild-type (WT). The concentrations of phytochelatin PC 2 in Osclt1 roots were only 32% and 12% of that in WT after As(V) and As(III) treatments, respectively. OsCLT1 mutation resulted in lower As accumulation in roots but higher As accumulation in shoots when exposed to As(V). Under As(III) treatment, Osclt1 accumulated a lower As concentration in roots but similar As concentration in shoots to WT. Further analysis showed that the reduction of As(V) to As(III) was decreased in Osclt1. Osclt1 was also hypersensitive to cadmium (Cd).These results indicate that OsCLT1 plays an important role in glutathione homeostasis, probably by mediating the export of c-glutamylcysteine and glutathione from plastids to the cytoplasm, which in turn affects As and Cd detoxification in rice.
Aim The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. Methods In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. Results The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. Conclusion The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.
LIR1 (LIGHT-INDUCED RICE1) encodes a 13-kD, chloroplast-targeted protein containing two nearly identical motifs of unknown function. LIR1 is present in the genomes of vascular plants, mosses, liverworts, and algae, but not in cyanobacteria. Using coimmunoprecipitation assays, pull-down assays, and yeast two-hybrid analyses, we showed that LIR1 interacts with LEAF-TYPE FERREDOXIN-NADP + OXIDOREDUCTASE (LFNR), an essential chloroplast enzyme functioning in the last step of photosynthetic linear electron transfer. LIR1 and LFNR formed high molecular weight thylakoid protein complexes with the TIC62 and TROL proteins, previously shown to anchor LFNR to the membrane. We further showed that LIR1 increases the affinity of LFNRs for TIC62 and that the rapid light-triggered degradation of the LIR1 coincides with the release of the LFNR from the thylakoid membrane. Loss of LIR1 resulted in a marked decrease in the accumulation of LFNR-containing thylakoid protein complexes without a concomitant decrease in total LFNR content. In rice (Oryza sativa), photosynthetic capacity of lir1 plants was slightly impaired, whereas no such effect was observed in Arabidopsis thaliana knockout mutants. The consequences of LIR1 deficiency in different species are discussed.
The transient receptor potential melastatin 2 (TRPM2) channel is associated with ischemia/reperfusion injury, inflammation, cancer, and neurodegenerative diseases. However, the limit of specific inhibitors impedes the development of TRPM2-targeted therapeutic agents. To discover more potent and selective TRPM2 inhibitors, 59 N-(p-amylcinnamoyl) anthranilic acid (ACA) derivatives were synthesized and evaluated using calcium imaging and electrophysiology approaches. Systematic structure–activity relationship studies resulted in some potent compounds inhibiting the TRPM2 channel with sub-micromolar half-maximal inhibitory concentration values. Among them, the preferred compound A23 exhibited TRPM2 selectivity over TRPM8 and TRPV1 channels as well as phospholipase A2 and showed neuroprotective activity in vitro. Following pharmacokinetic studies, A23 was further evaluated in a transient middle cerebral artery occlusion model in vivo, which significantly reduced cerebral infarction. These data indicate that A23 might serve as a useful tool for TRPM2-related research as well as a lead compound for the development of therapeutic agents for ischemic injury.
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