Publications by authors named "Qi-Hai Wang"

7 Publications

  • Page 1 of 1

Nicotinamide mononucleotide-elicited NAMPT signaling activation aggravated adjuvant-induced arthritis in rats by affecting peripheral immune cells differentiation.

Int Immunopharmacol 2021 Jun 12;98:107856. Epub 2021 Jun 12.

Department of Traditional Chinese Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu 241000, China; Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu 241000, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241000, China. Electronic address:

Supplement of nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD) has gained prominence due to the significant anti-aging potentials of nicotinamide phosphoribosyltransferas (NAMPT)/NAD signaling. Because over-expression of NAMPT is deeply implicated in inflammatory arthritis, we investigated the effects of NMN supplement on rats with adjuvant-induced arthritis (AIA). Tested rats were given oral treatment of NMN at 200 mg/kg/day for 25 days. Arthritis score and body weight were periodically recorded. Clinical outcomes were evaluated based on arthritic manifestations, ELISA analysis and histological examination. T cells subsets were analyzed by flow cytometry. Expressions of protein and mRNA were assessed by immunoblotting and PCR methods, respectively. Levels of CD172a, CD43, and NAMPT in peripheral blood mononuclear cells (PBMCs) were investigated by immunofluorescence approach. Obtained results were further validated by experiments in vitro. Generally, NMN exacerbated AIA severity in rats. It deteriorated MMP3-controlled tissues damages, and altered immune profile by increasing Th17/Treg cells ratio. The up-regulation of NAMPT in PBMCs from NMN-treated rats was confirmed by both immunofluorescence and PCR experiments, which was synchronized with significant increase in iNOS, MCP-1, IL-1β expression. NMN-primed AIA PBMCs were potent in up-regulating MCP-1, IL-1β, MMP3 and p-JNK expression in synovioblast. NMN stimulus barely affected Th17 cells count in in vitro cultured splenocytes, but it greatly potentiated the capability of AIA monocytes in inducing IL-17α secretion and Th17 cells differentiation in the co-cultured splenocytes. It suggested that long-term NMN supplement could exacerbate inflammatory arthritis by reshaping the immune milieu through the up-regulation of NAMPT.
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http://dx.doi.org/10.1016/j.intimp.2021.107856DOI Listing
June 2021

Proteomics research on the effects of applying selenium to apple leaves on photosynthesis.

Plant Physiol Biochem 2013 Sep 20;70:1-6. Epub 2013 May 20.

College of Horticulture, Henan Agricultural University, Zhengzhou 450002, China.

Untreated and Se-enriched apple leaves (Malus domestica Borkh. cv. 'Red Fuji') were used as the experimental materials. Proteomes of the differentially prepared tissues were compared through two-dimensional electrophoresis analysis and mass spectrum identification. There were 505 more protein spots in the proteome of the Se-enriched leaves than in the control leaves. Forty-seven protein spots were significantly differentially expressed (P < 0.05), among those, 32 protein spots were up-regulated while 12 protein points were down-regulated, and three new protein spots were found with the relative molecular masses of 31, 29, 26 kDa. Twenty-three protein spots with good shape and significant expression were selected for mass spectrometry analysis. These spots were excised from the gel and analyzed by a matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Peptide mass fingerprints (PMF) of all the proteins were submitted to NCBInr for protein identification, and 10 differential proteins were positively identified. Biological information of the identified proteins was found via http://www.uniprot.org/. There were three (1475, 1479, 1527) ribulose-1,5-bisphosphate carboxylase/oxygenase large subunits (Rubisco), two ribulose-1,5-bisphosphate carboxylases (346, 486) belonging to the Rubisco large chain family, one photosystem I reaction center subunit II (297), one chloroplast oxygen-evolving enhancer protein 1 (619), one Os12g0127100 protein whose function was unknown (927), one monodehydroascorbate reductase (1451), and one polyphenol oxidase V (1596). The major subcellular location for these proteins was the chloroplast, and they play important roles in photosynthesis and stress resistance for plants.
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http://dx.doi.org/10.1016/j.plaphy.2013.05.008DOI Listing
September 2013

Structure analysis of a new psychrophilic marine protease.

PLoS One 2011 23;6(11):e26939. Epub 2011 Nov 23.

Laboratory of Structural Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

A new psychrophilic marine protease was found from a marine bacterium Flavobacterium YS-80 in the Chinese Yellow Sea. The protease is about 49 kD with an isoelectric point about 4.5. It consists of 480 amino acids and is homologous to a psychrophilic alkaline protease (PAP) from an Antarctic Pseudomonas species. The protein was purified from the natural bacterium fermented and crystallized. Its crystal structure (PDB ID 3U1R) was solved at 2.0 Å by Molecular Replacement using a model based on PAP, and was refined to a crystallographic R(work) of 0.16 and an R(free) of 0.21. The marine protease consists of a two domain structure with an N-terminal domain including residues 37-264 and a C-terminal domain including residues 265-480. Similar to PAP, the N-terminal domain is responsible for proteolysis and the C-terminal is for stability. His186, His190, His196 and Tyr226 are ligands for the Zn(2+) ion in the catalytic center. The enzyme's Tyr226 is closer to the Zn(2+) ion than in PAP and it shows a stronger Zn(2+)-Tyr-OH bond. There are eight calcium ions in the marine protease molecule and they have significantly shorter bond distances to their ligands compared to their counterparts in all three crystal forms of PAP. On the other hand, the loops in the marine protease are more compact than in PAP. This makes the total structure stable and less flexible, resulting in higher thermo stability. These properties are consistent with the respective environments of the proteases. The structural analysis of this new marine protease provides new information for the study of psychrophilic proteases and is helpful for elucidating the structure-environment adaptation of these enzymes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026939PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223159PMC
April 2012

Cellular mechanisms underlying Hyperin-induced relaxation of rat basilar artery.

Fitoterapia 2011 Jun 12;82(4):626-31. Epub 2011 Feb 12.

Department of Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China.

Background And Aim: Hyperin, a flavonol compound extracted from the Chinese herb Abelmoschus manihot L. Medic, is reported to exert protective actions in cerebral ischemic injury. The specific aim of the present study was to study the relaxation of Hyperin in rat isolated basilar artery and identify the underlying cellular mechanisms.

Methods: Rat isolated basilar artery segments were cannulated and perfused while being superfused with PSS solution. Vessel images were recorded by video microscopy and diameters measured. Membrane potential was recorded using glass microelectrodes to evaluate the basilar artery smooth muscle cell hyperpolarization.

Results: Perfusion of Hyperin (1~100 μM) elicited a concentration-dependent relaxation of basilar artery segments preconstricted with 0.1 μM U46619. The response was significantly inhibited by the removal of the endothelium. Hyperin also elicited marked and concentration-dependent hyperpolarization of smooth muscle cells. 30 μM nitro-L-arginine (an inhibitor of nitric oxide synthase) and indomethacin (an inhibitor of cyclooxygenase), partially inhibited Hyperin-induced relaxation and hyperpolarization leaving an attenuated, but significant, endothelium-dependent relaxation and hyperpolarization. This remaining effect was almost completely blocked by 1mM tetraethylammonium (an inhibitor of Ca(2+)-activated K(+) channels), or by 100 μM DL-propargylglycine, an inhibitor of cystathionine-γ-lyase (a synthase of the endogenous H(2)S).

Conclusion: These findings show that Hyperin produces significant hyperpolarization in rat basilar artery smooth muscle cells and relaxation through both endothelium-dependent and endothelium-independent mechanisms. The underlying mechanisms appeared to be multi-factorial involving nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Our data further suggest that endogenous H(2)S is a component of the EDHF-mediated hyperpolarization and relaxation to Hyperin.
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http://dx.doi.org/10.1016/j.fitote.2011.01.023DOI Listing
June 2011

Functions, structures and Triton X-100 effect for the catalytic subunits of heterodimeric phospholipases A2 from Vipera nikolskii venom.

Toxicon 2009 Nov 3;54(6):709-16. Epub 2009 Jun 3.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.

Phospholipases A(2) (PLA(2)s) from snake venoms have diverse pharmacological functions including neurotoxicity, and more studies are necessary to understand relevant mechanisms. Here we report the different crystal structures for two enzymatically active basic subunits (HDP-1P and HDP-2P) of heterodimeric neurotoxic PLA(2)s isolated from Vipera nikolskii venom. Structural comparisons with similar PLA(2)s clearly show some flexible regions which might be important for the catalytic function and neurotoxicity. Unexpectedly, Triton X-100 molecule bound in the hydrophobic channel of HDP-1P and HDP-2P was observed, and its binding induced conformational changes in the Ca(2+) binding loop. Enzymatic activity measurements indicated that Triton X-100 decreased the activity of PLA(2), although with comparatively low inhibitory activity. For the first time exocytosis experiments in pancreatic beta cells were used to confirm the presynaptic neurotoxicity of relevant snake PLA(2). These experiments also indicated that Triton X-100 inhibited the influence of HDP-1P on exocytosis, but the inhibition was smaller than that of MJ33, a phospholipid-analogue inhibitor of PLA(2). Our studies performed at a cellular level are in good agreement with earlier findings that enzymatic activity of the snake presynaptic PLA(2) neurotoxins is essential for effective block of nerve terminals.
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http://dx.doi.org/10.1016/j.toxicon.2009.05.024DOI Listing
November 2009

Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis.

J Mol Biol 2007 Mar 16;366(5):1603-14. Epub 2006 Dec 16.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.

Phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities. It becomes an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway. Here, we report the crystal structure of human PAICS, the first in the entire PAICS family, at 2.8 A resolution. It revealed that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homo-octamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains. Based on structural comparison and functional complementation analyses, the active sites of SAICARs and AIRc were identified, including a putative substrate CO(2)-binding site. Furthermore, four symmetry-related, separate tunnel systems in the PAICS octamer were found that connect the active sites of AIRc and SAICARs. This study illustrated the octameric nature of the bifunctional enzyme. Each carboxylase active site is formed by structural elements from three AIRc domains, demonstrating that the octamer structure is essential for the carboxylation activity. Furthermore, the existence of the tunnel system implies a mechanism of intermediate channeling and suggests that the quaternary structure arrangement is crucial for effectively executing the sequential reactions. In addition, this study provides essential structural information for designing PAICS-specific inhibitors for use in cancer chemotherapy.
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http://dx.doi.org/10.1016/j.jmb.2006.12.027DOI Listing
March 2007

Crystal structure of the diadenosine tetraphosphate hydrolase from Shigella flexneri 2a.

Proteins 2006 Dec;65(4):1032-5

Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

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http://dx.doi.org/10.1002/prot.21106DOI Listing
December 2006
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