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1.  Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia 
Scientific Reports  2016;6:37033.
Post-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity.
PMCID: PMC5109474  PMID: 27845401
2.  NMDA receptor signaling: death or survival? 
Frontiers in biology  2011;6(6):468-476.
Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl-D-aspartate (NMDA) receptors. Conversely, normal physiological brain function and neuronal survival require adequate activation of NMDA receptors. Studies have revealed that NMDA receptor-induced neuronal death or survival is mediated through distinct subset of NMDA receptors triggering different intracellular signaling pathways. Here we discuss recent advances in the characterization of NMDA receptors in neuronal protection, emphasizing subunit-specific role, which contributes to temporal-spatial distribution, subcellular localization and diverse channel properties of NMDA receptors.
PMCID: PMC3491906  PMID: 23144645
NMDA receptors; glutamate; excitotoxicity; ischemia; neuroprotection
3.  Arabidopsis WRKY6 Transcription Factor Acts as a Positive Regulator of Abscisic Acid Signaling during Seed Germination and Early Seedling Development 
PLoS Genetics  2016;12(2):e1005833.
The phytohormone abscisic acid (ABA) plays important roles during seed germination and early seedling development. Here, we characterized the function of the Arabidopsis WRKY6 transcription factor in ABA signaling. The transcript of WRKY6 was repressed during seed germination and early seedling development, and induced by exogenous ABA. The wrky6-1 and wrky6-2 mutants were ABA insensitive, whereas WRKY6-overexpressing lines showed ABA-hypersensitive phenotypes during seed germination and early seedling development. The expression of RAV1 was suppressed in the WRKY6-overexpressing lines and elevated in the wrky6 mutants, and the expression of ABI3, ABI4, and ABI5, which was directly down-regulated by RAV1, was enhanced in the WRKY6-overexpressing lines and repressed in the wrky6 mutants. Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that WRKY6 could bind to the RAV1 promoter in vitro and in vivo. Overexpression of RAV1 in WRKY6-overexpressing lines abolished their ABA-hypersensitive phenotypes, and the rav1 wrky6-2 double mutant showed an ABA-hypersensitive phenotype, similar to rav1 mutant. Together, the results demonstrated that the Arabidopsis WRKY6 transcription factor played important roles in ABA signaling by directly down-regulating RAV1 expression.
Author Summary
The WRKY6 protein is a WRKY transcription factor which plays important roles in plant pathogen defense, phosphate translocation, and arsenate resistance. This study demonstrated that the expression of WRKY6 was obviously repressed during seed germination and significantly induced by exogenous ABA. In the presence of exogenous ABA, the two wrky6 mutants showed ABA-insensitive phenotypes, whereas the WRKY6-overexpressing lines were hypersensitive to ABA. The WRKY6 transcription factor repressed RAV1 expression and enhanced the expression of ABI3, ABI4 and ABI5, which was down-regulated by RAV1. The WRKY6 protein could bind to the W-box motif within the RAV1 promoter, indicating that WRKY6 directly regulated RAV1 expression. Overexpression of RAV1 abolished the ABA-sensitivity of WRKY6-overexpressing lines, and repression of RAV1 impaired the ABA-insensitivity of wrky6 mutants. Our results reveal the important roles of WRKY6 in ABA signaling during seed germination and early seedling development.
PMCID: PMC4734665  PMID: 26829043
4.  The Saccharomyces cerevisiae Chromatin Remodeler Fun30 Regulates DNA End Resection and Checkpoint Deactivation 
Molecular and Cellular Biology  2012;32(22):4727-4740.
Fun30 is a Swi2/Snf2 homolog in budding yeast that has been shown to remodel chromatin both in vitro and in vivo. We report that Fun30 plays a key role in homologous recombination, by facilitating 5′-to-3′ resection of double-strand break (DSB) ends, apparently by facilitating exonuclease digestion of nucleosome-bound DNA adjacent to the DSB. Fun30 is recruited to an HO endonuclease-induced DSB and acts in both the Exo1-dependent and Sgs1-dependent resection pathways. Deletion of FUN30 slows the rate of 5′-to-3′ resection from 4 kb/h to about 1.2 kb/h. We also found that the resection rate is reduced by DNA damage-induced phosphorylation of histone H2A-S129 (γ-H2AX) and that Fun30 interacts preferentially with nucleosomes in which H2A-S129 is not phosphorylated. Fun30 is not required for later steps in homologous recombination. Like its homolog Rdh54/Tid1, Fun30 is required to allow the adaptation of DNA damage checkpoint-arrested cells with an unrepaired DSB to resume cell cycle progression.
PMCID: PMC3486187  PMID: 23007155
5.  Transcriptome analysis of rice root responses to potassium deficiency 
BMC Plant Biology  2012;12:161.
Potassium (K+) is an important nutrient ion in plant cells and plays crucial roles in many plant physiological and developmental processes. In the natural environment, K+ deficiency is a common abiotic stress that inhibits plant growth and reduces crop productivity. Several microarray studies have been conducted on genome-wide gene expression profiles of rice during its responses to various stresses. However, little is known about the transcriptional changes in rice genes under low-K+ conditions.
We analyzed the transcriptomic profiles of rice roots in response to low-K+ stress. The roots of rice seedlings with or without low-K+ treatment were harvested after 6 h, and 3 and 5 d, and used for microarray analysis. The microarray data showed that many genes (2,896) were up-regulated or down-regulated more than 1.2-fold during low-K+ treatment. GO analysis indicated that the genes showing transcriptional changes were mainly in the following categories: metabolic process, membrane, cation binding, kinase activity, transport, and so on. We conducted a comparative analysis of transcriptomic changes between Arabidopsis and rice under low-K+ stress. Generally, the genes showing changes in transcription in rice and Arabidopsis in response to low-K+ stress displayed similar GO distribution patterns. However, there were more genes related to stress responses and development in Arabidopsis than in rice. Many auxin-related genes responded to K+ deficiency in rice, whereas jasmonic acid-related enzymes may play more important roles in K+ nutrient signaling in Arabidopsis.
According to the microarray data, fewer rice genes showed transcriptional changes in response to K+ deficiency than to phosphorus (P) or nitrogen (N) deficiency. Thus, transcriptional regulation is probably more important in responses to low-P and -N stress than to low-K+ stress. However, many genes in some categories (protein kinase and ion transporter families) were markedly up-regulated, suggesting that they play important roles during K+ deficiency. Comparative analysis of transcriptomic changes between Arabidopsis and rice showed that monocots and dicots share many similar mechanisms in response to K+ deficiency, despite some differences. Further research is required to clarify the differences in transcriptional regulation between monocots and dicots.
PMCID: PMC3489729  PMID: 22963580
Rice; K+ deficiency; microarray; transcriptome
6.  Effects of erythromycin on voriconazole pharmacokinetics and association with CYP2C19 polymorphism 
To assess the impacts of erythromycin on the pharmacokinetics of voriconazole and its association with CYP2C19 genotypes in healthy Chinese male subjects.
A single-center, open, crossover clinical study with two treatment phases was carried out. Eighteen healthy male volunteers, including 6 CYP2C19 homozygous extensive metabolizers (EMs, *1/*1), 6 heterozygous EMs (HEMs, *1/*2 or *1/*3), and 6 CYP2C19 poor metabolizers (PMs, *2/*2 or *2/*3), were enrolled in this study. A single oral dose of 200 mg voriconazole was administrated to all subjects after 3-day pretreatment with either 500 mg erythromycin or placebo three times daily. Periods were separated by a washout period of 14 days. Serial venous blood samples were collected, and plasma concentrations of voriconazole were determined by HPLC.
Cmax, AUC0–24, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\hbox{AU}}{{\hbox{C}}_{0 - \infty }} $$\end{document} of voriconazole were increased significantly, while oral clearance of voriconazole was decreased significantly by erythromycin administration (p < 0.001, respectively). Compared with individuals with CYP2C19 PM genotypes, individuals with CYP2C19 EM and HEM genotypes showed significantly decreased T½, AUC0–24, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\hbox{AU}}{{\hbox{C}}_{0 - \infty }} $$\end{document}, and increased oral clearance of voriconazole (p < 0.05, respectively). In addition, significant increases in AUC0–24 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\hbox{AU}}{{\hbox{C}}_{0 - \infty }} $$\end{document} and decreases in oral clearance of voriconazole after erythromycin treatment were observed in CYP2C19 HEMs and PMs (p < 0.05, respectively), but not in CYP2C19 EMs.
Both CYP2C19 genotypes and CYP3A4 inhibitor erythromycin can influence the plasma concentration of voriconazole, and erythromycin increases plasma concentration of voriconazole in a CYP2C19 genotype-dependent manner.
PMCID: PMC2957581  PMID: 20669013
Voriconazole; Erythromycin; CYP2C19; Genetic polymorphism; Chinese
7.  Ion transporters involved in pollen germination and pollen tube tip-growth 
Plant Signaling & Behavior  2009;4(12):1193-1195.
Pollen germination (PG) and pollen tube growth (PTG) play crucial roles in sexual reproduction of flowering plants by sending sperm cells to the ovule. These two processes are regarded as ideal model system for the study of cell signaling and cell polarized growth. It has been considered for a long time that ion transports across the pollen tube membranes are essential for pollen tube navigation and growth. Previous transcriptome analyses for Arabidopsis have shown that the transcripts related to cellular transport are correspondingly overrepresented during the process of pollen tube growth. Here, we showed that 459 transporter genes expressed during PG and PTG in Arabidopsis. In addition, the gene expression profiles of ion (including Ca2+, H+, K+, Cl−) channels and transporters were further analyzed. This analysis provides novel information for the potential candidate genes involving in ion fluxes across the pollen tube membranes and in regulation of pollen tube tip growth.
PMCID: PMC2819455  PMID: 20514245
Arabidopsis; microarray; pollen germination; pollen tube growth; channel; transporter

Results 1-7 (7)