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Li D.,Beijing Institute of Biotechnology | Dong Q.,Beijing Institute of Biotechnology | Tao Q.,Anhui University | Gu J.,Beijing Institute of Biotechnology | And 10 more authors.
Cell Reports | Year: 2015

The ubiquitin-proteasome system is a vital proteolytic pathway required for cell homeostasis. However, the turnover mechanism of the proteasome subunit itself is still not understood. Here, we show that the 20S proteasome subunit PSMA7 is subjected to ubiquitination and proteasomal degradation, which was suppressed by PSMA7 phosphorylation at Y106 mediated by the nonreceptor tyrosine kinases c-Abl/Arg. BRCA1 specifically functions as an E3 ubiquitin ligase of PSMA7 ubiquitination. c-Abl/Arg regulates cellular proteasome abundance by controlling the PSMA7 subunit supply. Downregulated PSMA7 level results in decreased proteasome abundance inc-Abl/Arg RNAi-knockdown or c-abl/. arg-deficient cells, which demonstrated an increased sensitivity to proteasome inhibition. In response to oxidative stress, the c-Abl-mediated upregulation of proteasome level compensates for the proteasomal activity impairment induced by reactive oxygen species. Abl-kinases-regulated biogenesis and homeostasis of proteasome complexes may be important for understanding related diseases and pathological states. © 2015 The Authors. Source


Yang H.,China Institute of Technology | Zhang W.,China Institute of Technology | Kong Q.,Pharmaron Preclinical Services Laboratories | Liu H.,China Institute of Technology | And 4 more authors.
Food and Chemical Toxicology | Year: 2013

Thiazole-Zn is a newly chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters. To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used. Postnatal days (PND) 22-old Sprague-Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200. mg/kg/day for 20. days. The thyroid endpoints and development endpoints were assessed. The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40. mg/kg thiazole-Zn, but had no difference from controls at the other doses. Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell. No histological changes were observed in any of the other observed organs. In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups. These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity. © 2012 Elsevier Ltd. Source


Yuxia W.,Beijing Institute of Pharmacology and Toxicology | Lijun Y.,Beijing Institute of Pharmacology and Toxicology | Lijun Y.,Beijing Institute of Disease Control and Prevention | Qin L.,Beijing Institute of Pharmacology and Toxicology | And 2 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2011

A simple, fast, sensitive and robust method for the determination of the sulfur mustard (SM) exposure biomarker-N 7-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (HETEG) was reported using high-performance liquid chromatography-positive electrospray tandem mass spectrometry (HPLC-ESI-MS/MS), working in multiple reaction monitor (MRM) mode. The method provided limit of detection of 0.330ng/mL and lower limit of quantitation of 0.940ng/mL. The method was linearly calibrated from 0.940ng/mL to 587ng/mL with precisions of 3.5-14.5%, and accuracies of 88-112%. The recovery varied from 102% to 118%. HETEG spiked in DNA hydrolytes isolated from the human whole blood was stable after five freeze/thaw cycles and 35-day frozen at -20°C. For the exposed biological samples, alkylated DNA was isolated from SM-treated human whole blood, followed by DNA digestion and adducts enrichment, the resulting alkylation base was determined. By the procedure, the HETEG level in DNA hydrolytes isolated from the human whole blood exposure to 312ng/mL SM was detected successfully. © 2011 Elsevier B.V. Source


Wei Q.-H.,Beijing Institute of Pharmacology and Toxicology | Wei Q.-H.,Beijing Institute of Disease Control and Prevention | Wu N.,Beijing Institute of Pharmacology and Toxicology | Bian J.-M.,Beijing Institute of Pharmacology and Toxicology | And 3 more authors.
Addiction Biology | Year: 2013

Drug addiction is thought to result from an intractable and aberrant learning and memory in response to drug-related stimulation, and cholinergic neurotransmission plays an important role in this process. Phosphatidylethanolamine-binding protein (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP), an 11 amino acid peptide that enhances the production of choline acetyltransferase (ChAT) and assists in the development of cholinergic projections from the medial septal nuclei to the hippocampus. However, whether PEBP is involved in drug addiction remains unclear. In the present study, PEBP expression in the hippocampus, as detected by proteomics analysis, was found to be dramatically up-regulated after rats received chronic morphine treatment. Western blotting analysis revealed a specific up-regulation of PEBP expression in the hippocampus but not in any other brain regions assessed. A down-regulation of hippocampal PEBP levels induced by antisense oligodeoxynucleotides resulted in aggravated morphine dependence. Together, these findings indicate that PEBP is involved in morphine dependence. Moreover, the time course of PEBP expression changes and ChAT activity was investigated during chronic morphine treatment and withdrawal. The results showed that the hippocampal PEBP levels were up-regulated during chronic morphine treatment and returned to the baseline 3 days after withdrawal, after which PEBP levels were persistently up-regulated for 28 days after withdrawal. The changes in hippocampal ChAT activity followed a pattern that was similar to that of the PEBP levels. Taken together, these results suggest that hippocampal PEBP is involved in morphine dependence and withdrawal, perhaps through modulating cholinergic transmission in the hippocampus. © 2011 Society for the Study of Addiction. Source


Wang Y.,Beijing Institute of Disease Control and Prevention
Journal of bacteriology | Year: 2012

Brucella canis is considered a rare cause of human brucellosis because of difficulties in presumptive diagnosis and underestimation of the incidence. Here, we report the draft genome sequence of a Brucella canis isolate, BCB018, isolated from a human patient, providing precious resources for comparative genomics analysis of Brucella field strains. Source

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