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961.
Iron scarcity is one of the nutrition limitations that the Gram-positive infectious pathogens Streptococcus pneumoniae encounter in the human host. To guarantee sufficient iron supply, the ATP binding cassette (ABC) transporter Pia is employed to uptake iron chelated by hydroxamate siderophore, via the membrane-anchored substrate-binding protein PiaA. The high affinity towards ferrichrome enables PiaA to capture iron at a very low concentration in the host. We presented here the crystal structures of PiaA in both apo and ferrichrome-complexed forms at 2.7 and 2.1 Å resolution, respectively. Similar to other class III substrate binding proteins, PiaA is composed of an N-terminal and a C-terminal domain bridged by an α-helix. At the inter-domain cleft, a molecule of ferrichrome is stabilized by a number of highly conserved residues. Upon ferrichrome binding, two highly flexible segments at the entrance of the cleft undergo significant conformational changes, indicating their contribution to the binding and/or release of ferrichrome. Superposition to the structure of Escherichia coli ABC transporter BtuF enabled us to define two conserved residues: Glu119 and Glu262, which were proposed to form salt bridges with two arginines of the permease subunits. Further structure-based sequence alignment revealed that the ferrichrome binding pattern is highly conserved in a series of PiaA homologs encoded by both Gram-positive and negative bacteria, which were predicted to be sensitive to albomycin, a sideromycin antibiotic derived from ferrichrome. 相似文献
962.
Wang-Qing Chen Yan Shu Qing Li Lin-Yong Xu Mary W. Roederer Lan Fan Lan-Xiang Wu Fa-Zhong He Jian-Quan Luo Zhi-Rong Tan Yi-Jing He Hong-Hao Zhou Xiang Chen Wei Zhang 《PloS one》2013,8(8)
Background
The pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males.Method
A total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP) were measured up to 48 h.Result
In this study, the area under the plasma concentration-time curve (AUC) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC(0–48) (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033), AUC(0–∞) (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016), and the change(%) of the diastolic blood pressure (DBP) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026). This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(%) in our trial.Conclusion
The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(%) from the baseline compared with the wild-type.Trial Registration
Chinese Clinical Trial Registry ChiCTR-TNC-10000898 相似文献963.
Genta Kakiyama Dalila Marques Rebecca Martin Hajime Takei Daniel Rodriguez-Agudo Sandra A. LaSalle Taishi Hashiguchi Xiaoying Liu Richard Green Sandra Erickson Gregorio Gil Michael Fuchs Mitsuyoshi Suzuki Tsuyoshi Murai Hiroshi Nittono Phillip B. Hylemon Huiping Zhou William M. Pandak 《Journal of lipid research》2020,61(12):1629
NAFLD is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to NASH remain unclear. This lack of knowledge leads to a decreased ability to find relevant animal models, predict disease progression, or develop clinical treatments. In the current study, we used multiple mouse models of NAFLD, human correlation data, and selective gene overexpression of steroidogenic acute regulatory protein (StarD1) in mice to elucidate a plausible mechanistic pathway for promoting the transition from NAFL to NASH. We show that oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the “acidic/alternative” pathway of cholesterol metabolism. Specifically, we report data showing that an inability to upregulate CYP7B1, in the setting of insulin resistance, results in the accumulation of toxic intracellular cholesterol metabolites that promote inflammation and hepatocyte injury. This metabolic pathway, initiated and exacerbated by insulin resistance, offers insight into approaches for the treatment of NAFLD. 相似文献
964.
Kumar P. S. Ling C. Y. Zhou Z. B. Dong Y. L. Sun C. L. Song Y. X. Wong N. K. Ju J. H. 《Microbiology》2020,89(4):483-492
Microbiology - Marine actinobacteria particularly from marine environments are believed to be inexhaustible sources of biologically active molecules for biomedical and industrial applications. We... 相似文献
965.
Jing Zhang Mingjian Zhou Zhenglin Ge Jie Shen Can Zhou Cecilia Gotor Luis C. Romero Xingliang Duan Xin Liu Deliang Wu Xianchao Yin Yanjie Xie 《Plant, cell & environment》2020,43(3):624-636
Recent studies have demonstrated that hydrogen sulfide (H2S) produced through the activity of l -cysteine desulfhydrase (DES1) is an important gaseous signaling molecule in plants that could participate in abscisic acid (ABA)-induced stomatal closure. However, the coupling of the DES1/H2S signaling pathways to guard cell movement has not been thoroughly elucidated. The results presented here provide genetic evidence for a physiologically relevant signaling pathway that governs guard cell in situ DES1/H2S function in stomatal closure. We discovered that ABA-activated DES1 produces H2S in guard cells. The impaired guard cell ABA phenotype of the des1 mutant can be fully complemented when DES1/H2S function has been specifically rescued in guard cells and epidermal cells, but not mesophyll cells. This research further characterized DES1/H2S function in the regulation of LONG HYPOCOTYL1 (HY1, a member of the heme oxygenase family) signaling. ABA-induced DES1 expression and H2S production are hyper-activated in the hy1 mutant, both of which can be fully abolished by the addition of H2S scavenger. Impaired guard cell ABA phenotype of des1/hy1 can be restored by H2S donors. Taken together, this research indicated that guard cell in situ DES1 function is involved in ABA-induced stomatal closure, which also acts as a pivotal hub in regulating HY1 signaling. 相似文献
966.
Xu Feng Peng Feng Huilin Yu Xingyu Yu Qi Sun Siyu Liu Thuy Nguyen Minh Jun Chen Di Wang Qing Zhang Lei Cao Changmei Zhou Qiang Li Jialei Xiao Shihua Zhong Aoxue Wang Lijuan Wang Hongyu Pan Xiaodong Ding 《Plant, cell & environment》2020,43(5):1192-1211
Although the function and regulation of SnRK1 have been studied in various plants, its molecular mechanisms in response to abiotic stresses are still elusive. In this work, we identified an AP2/ERF domain-containing protein (designated GsERF7) interacting with GsSnRK1 from a wild soybean cDNA library. GsERF7 gene expressed dominantly in wild soybean roots and was responsive to ethylene, salt, and alkaline. GsERF7 bound GCC cis-acting element and could be phosphorylated on S36 by GsSnRK1. GsERF7 phosphorylation facilitated its translocation from cytoplasm to nucleus and enhanced its transactivation activity. When coexpressed in the hairy roots of soybean seedlings, GsSnRK1(wt) and GsERF7(wt) promoted plants to generate higher tolerance to salt and alkaline stresses than their mutated species, suggesting that GsSnRK1 may function as a biochemical and genetic upstream kinase of GsERF7 to regulate plant adaptation to environmental stresses. Furthermore, the altered expression patterns of representative abiotic stress-responsive and hormone-synthetic genes were determined in transgenic soybean hairy roots after stress treatments. These results will aid our understanding of molecular mechanism of how SnRK1 kinase plays a cardinal role in regulating plant stress resistances through activating the biological functions of downstream factors. 相似文献
967.
968.
Zhenyuan Gao Hairong Zhou Yaping Wang Juan Chen Yimei Ou 《Journal of cellular biochemistry》2020,121(1):332-343
This investigation was intended to elucidate whether long noncoding RNA (lncRNA)-activated by transforming growth factor-β (ATB) interacting with miR-200c could mediate colorectal cancer (CRC) progression, offering potential strategies for diagnosing and treating CRC. Here totally 315 patients with CRC were recruited, and their CRC tissues and adjacent normal tissues were gathered. Concurrently, four colon cancer cell lines (ie, SW620, Lovo, HCT116, and SW480) and the human colon mucosal epithelial cell line (NCM460) were also purchased. Moreover, si-ATB, si-NC, miR-200c mimic, miR-200c inhibitor, and miR-NC were prepared for transfection into the CRC cells, and their effects on CRC cell lines were evaluated based on the conduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and flow cytometry assay. Eventually, the Luciferase reporter gene assay was carried out to judge if there existed a targeted relationship between ATB and miR-200c. The results of Cox regression analyses suggested that overexpressed lncRNA ATB, underexpressed miR-200c, poor tumor differentiation, lymph-vascular invasion, and perineural invasion were symbolic of shortened survival of the patients with CRC (all P < .05). Besides, transfection of pcDNA3.1-ATB and miR-200c inhibitor could boost the viability and proliferation of Lovo and SW620 cell lines (all P < .05). Meanwhile, the expressions of p53 and p21 were also reduced under treatments of pcDNA3.1-ATB and miR-200c inhibitor (P < .05). In addition, CDK2 seemed to reverse the contribution of miR-200c to intensifying viability and proliferation of Lovo and SW420 cell lines (P < .05). Furthermore, ATB might downregulate miR-200c expression by targeting it (P < .05), and CDK2 was subjected to dual regulation of both ATB and miR-200c (P < .05). In conclusion, the lncRNA ATB/miR-200c/CDK2 signaling was responsible for intensified proliferation and prohibited apoptosis of CRC cells, which might provide effective approaches for diagnosing and treating CRC. 相似文献
969.
970.