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941.
Kaifeng Guo Junxi Lu Yan Huang Mian Wu Lei Zhang Haoyong Yu Mingliang Zhang Yuqian Bao John Cijiang He Haibing Chen Weiping Jia 《PloS one》2015,10(4)
The overproduction of mitochondrial reactive oxygen species (ROS) plays a key role in the pathogenesis of diabetic nephropathy (DN). However, the underlying molecular mechanism remains unclear. Our aim was to investigate the role of PGC-1α in the pathogenesis of DN. Rat glomerular mesangial cells (RMCs) were incubated in normal or high glucose medium with or without the PGC-1α-overexpressing plasmid (pcDNA3-PGC-1α) for 48 h. In the diabetic rats, decreased PGC-1α expression was associated with increased mitochondrial ROS generation in the renal cortex, increased proteinuria, glomerular hypertrophy, and higher glomerular 8-OHdG (a biomarker for oxidative stress). In vitro, hyperglycemia induced the downregulation of PGC-1α, which led to increased DRP1 expression, increased mitochondrial fragmentation and damaged network structure. This was associated with an increase in ROS generation and mesangial cell hypertrophy. These pathological changes were reversed in vitro by the transfection of pcDNA3-PGC-1α. These data suggest that PGC-1α may protect DN via the inhibition of DRP1-mediated mitochondrial dynamic remodeling and ROS production. These findings may assist the development of novel therapeutic strategies for patients with DN. 相似文献
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944.
Gui-lai Zuo Lian-fang Zhang Jin Qi Hui Kang Peng Jia Hao Chen Xing Shen Lei Guo Han-bing Zhou Jin-shen Wang Qi Zhou Nian-dong Qian Lian-fu Deng 《PloS one》2015,10(3)
The hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, are the central mediators of the homeostatic response that enables cells to survive and differentiate in low-oxygen conditions. Previous studies indicated that disruption of the von Hippel-Lindau gene (Vhl) coincides with the activation of HIFα signaling. Here we show that inactivation of Vhl in mature osteoblasts/osteocytes induces their apoptosis and disrupts the cell/canalicular network. VHL-deficient (ΔVHL) mice exhibited a significantly increased cortical bone area resulting from enhanced proliferation and osteogenic differentiation of the bone marrow stromal cells (BMSCs) by inducing the expression of β-catenin in the BMSC. Our data suggest that the VHL/HIFα pathway in mature osteoblasts/osteocytes plays a critical role in the bone cell/canalicular network and that the changes of osteocyte morphology/function and cell/canalicular network may unleash the bone formation, The underlying mechanism of which was the accumulation of β-catenin in the osteoblasts/osteoprogenitors of the bone marrow. 相似文献
945.
Xiu‐feng Zhang Lei Chen Qian‐fan Yang Qian Li Xiao‐ran Sun Hong‐bo Chen Guang Yang Ya‐lin Tang 《Luminescence》2015,30(8):1176-1183
Complexation between the primary carrier of ligands in blood plasma, human serum transferrin (Tf), and a cyanine dye, 3,3′‐di(3‐sulfopropyl)‐4,5,4′,5′‐dibenzo‐9‐phenyl‐thiacarbocyanine‐triethylam monium salt (PTC) was investigated using fluorescence spectra, UV/Vis absorption spectra, synchronous fluorescence spectra, circular dichroism (CD) and molecular dynamic docking. The experimental results demonstrate that the formation of PTC–Tf complex is stabilized by van der Waal's interactions and hydrogen bonds, and the binding constants were found to be 8.55 × 106, 8.19 × 106 and 1.75 × 104 M?1. Moreover, fluorescence experiments prove that the operational mechanism for the fluorescence quenching is static quenching and non‐radiative energy transfer. Structural investigation of the PTC–Tf complexes via synchronous fluorescence spectra and CD showed that the structure of Tf became more stable with a major increase in the α‐helix content and increased polarity around the tryptophan residues after PTC binding. In addition, molecular modeling highlights the residues located in the N‐lobe, which retain high affinity for PTC. The mode of action of the PTC–Tf complex is illustrated by these results, and may provide an effective pathway for the transport and targeted delivery of antitumor agents. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
946.
The non-selective apoplastic passage of Cu and Cu-citrate complexes into the root stele of monocotyledonous corn and dicotyledonous soybean was investigated using an inorganic-salt-precipitation technique. Either Cu ions or Cu-citrate complexes were drawn into root through the apoplast from the root growth medium, and K4[Fe(CN)6] was subsequently perfused through xylem vessels or the entire root cross section. Based on microscopic identification of the reddish-brown precipitates of copper ferrocyanide in the cell walls of the xylem of corn and soybean roots, Cu2+ passed through the endodermal barrier into the xylem of both species. When the solution containing 200 μM CuSO4 and 400 μM sodium citrate (containing 199.98 μM Cu-citrate, 0.02 μM Cu2+) was drawn via differential pressure gradients into the root xylem while being perfused with K4[Fe(CN)6] through the entire root cross-section, reddish-brown precipitates were observed in the walls of the stele of soybean, but not corn root. However, when a CuSO4 solution containing 0.02 or 0.2 μM free Cu2+ was used, no reddish-brown precipitates were detected in the stele of either of the two plants. Results indicated that endodermis was permeable to Cu-citrate complexes in primary roots of soybean, but not corn. The permeability of the endodermal barrier to the Cu-citrate complex may vary between dicotyledonous and monocotyledonous plants, which has considerable implications for chelant-enhanced phytoextraction. 相似文献
947.
Generation of a tamoxifen inducible Tnnt2MerCreMer knock‐in mouse model for cardiac studies
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Jianyun Yan Nishat Sultana Lu Zhang David S. Park Akshay Shekhar Jun Hu Lei Bu Chen‐Leng Cai 《Genesis (New York, N.Y. : 2000)》2015,53(6):377-386
Tnnt2, encoding thin‐filament sarcomeric protein cardiac troponin T, plays critical roles in heart development and function in mammals. To develop an inducible genetic deletion strategy in myocardial cells, we generated a new Tnnt2:MerCreMer (Tnnt2MerCreMer/+) knock‐in mouse. Rosa26 reporter lines were used to examine the specificity and efficiency of the inducible Cre recombinase. We found that Cre was specifically and robustly expressed in the cardiomyocytes at embryonic and adult stages following tamoxifen induction. The knock‐in allele on Tnnt2 locus does not impact cardiac function. These results suggest that this new Tnnt2MerCreMer/+ mouse could be applied towards the temporal genetic deletion of genes of interests in cardiomyocytes with Cre‐LoxP technology. The Tnnt2MerCreMer/+ mouse model also provides a useful tool to trace myocardial lineage during development and repair after cardiac injury. genesis 53:377–386, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
948.
Plasma folate levels in early to mid pregnancy after a nation‐wide folic acid supplementation program in areas with high and low prevalence of neural tube defects in china
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949.
Lei Gao Dantong Li Ke Ma Wenjuan Zhang Tao Xu Cong Fu Changbin Jing Xiaoe Jia Shuang Wu Xin Sun Mei Dong Min Deng Yi Chen Wenge Zhu Jinrong Peng Fengyi Wan Yi Zhou Leonard I. Zon Weijun Pan 《PLoS genetics》2015,11(7)
In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion. In this process, well-established DNA damage response pathways are vital to resolve the replication stress, which is deleterious for genome stability and cell survival. However, the detailed mechanism on the response and repair of the replication stress-induced DNA damage during hematopoietic progenitor expansion remains elusive. Here we report that a novel zebrafish mutantcas003 with nonsense mutation in topbp1 gene encoding topoisomerase II β binding protein 1 (TopBP1) exhibits severe definitive hematopoiesis failure. Homozygous topbp1cas003 mutants manifest reduced number of HSPCs during definitive hematopoietic cell expansion, without affecting the formation and migration of HSPCs. Moreover, HSPCs in the caudal hematopoietic tissue (an equivalent of the fetal liver in mammals) in topbp1cas003 mutant embryos are more sensitive to hydroxyurea (HU) treatment. Mechanistically, subcellular mislocalization of TopBP1cas003 protein results in ATR/Chk1 activation failure and DNA damage accumulation in HSPCs, and eventually induces the p53-dependent apoptosis of HSPCs. Collectively, this study demonstrates a novel and vital role of TopBP1 in the maintenance of HSPCs genome integrity and survival during hematopoietic progenitor expansion. 相似文献
950.