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91.
Lin-Lin Jia Yu-Ming Kang Fu-Xin Wang Hong-Bao Li Yan Zhang Xiao-Jing Yu Jie Qi Yu-Ping Suo Zhen-Jun Tian Zhiming Zhu Guo-Qing Zhu Da-Nian Qin 《PloS one》2014,9(1)
Aims
Regular exercise as an effective non-pharmacological antihypertensive therapy is beneficial for prevention and control of hypertension, but the central mechanisms are unclear. In this study, we hypothesized that chronic exercise training (ExT) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and restoring the neurotransmitters balance in the hypothalamic paraventricular nucleus (PVN) in young spontaneously hypertensive rats (SHR). In addition, we also investigated the involvement of nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in exercise-induced effects.Methods and results
Moderate-intensity ExT was administrated to young normotensive Wistar-Kyoto (WKY) and SHR rats for 16 weeks. SHR rats had a significant increase in mean arterial pressure and cardiac hypertrophy. SHR rats also had higher levels of glutamate, norepinephrine (NE), phosphorylated IKKβ, NF-κB p65 activity, NAD(P)H oxidase subunit gp91phox, PICs and the monocyte chemokine protein-1 (MCP-1), and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN. These SHR rats also exhibited higher renal sympathetic nerve activity (RSNA), and higher plasma levels of PICs, and lower plasma IL-10. However, ExT ameliorates all these changes in SHR rats.Conclusion
These findings suggest that there are the imbalances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN of SHR rats, which at least partly contributing to sympathoexcitation, hypertension and cardiac hypertrophy; chronic exercise training attenuates hypertension and cardiac hypertrophy by restoring the balances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN; NF-κB and oxidative stress in the PVN may be involved in these exercise-induced effects. 相似文献92.
Ling-Ling Sun Ming Li Fang Suo Xiao-Man Liu En-Zhi Shen Bing Yang Meng-Qiu Dong Wan-Zhong He Li-Lin Du 《PLoS genetics》2013,9(8)
Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in animal development and human diseases. Molecular understanding of autophagy has mainly come from the budding yeast Saccharomyces cerevisiae, and it remains unclear to what extent the mechanisms are the same in other organisms. Here, through screening the mating phenotype of a genome-wide deletion collection of the fission yeast Schizosaccharomyces pombe, we obtained a comprehensive catalog of autophagy genes in this highly tractable organism, including genes encoding three heretofore unidentified core Atg proteins, Atg10, Atg14, and Atg16, and two novel factors, Ctl1 and Fsc1. We systematically examined the subcellular localization of fission yeast autophagy factors for the first time and characterized the phenotypes of their mutants, thereby uncovering both similarities and differences between the two yeasts. Unlike budding yeast, all three Atg18/WIPI proteins in fission yeast are essential for autophagy, and we found that they play different roles, with Atg18a uniquely required for the targeting of the Atg12–Atg5·Atg16 complex. Our investigation of the two novel factors revealed unforeseen autophagy mechanisms. The choline transporter-like protein Ctl1 interacts with Atg9 and is required for autophagosome formation. The fasciclin domain protein Fsc1 localizes to the vacuole membrane and is required for autophagosome-vacuole fusion but not other vacuolar fusion events. Our study sheds new light on the evolutionary diversity of the autophagy machinery and establishes the fission yeast as a useful model for dissecting the mechanisms of autophagy. 相似文献
93.
Shi-Jun Li Jian-An Wang Jing Li Dan Suo 《Preparative biochemistry & biotechnology》2013,43(4):334-347
Abstract The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide, Z-Asp-Val-NH2 of thymopentin (TP-5), in organic solvents was studied. Z-Asp-OMe and Val-NH2 were used as the acyl donor and the nucleophile, respectively. An industrial alkaline protease alcalase was used to catalyze the synthesis of the target dipeptide in water-organic cosolvent systems. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including organic solvents, water content, temperature, pH, and reaction time on the yield of Z-Asp-Val-NH2. The optimum conditions using alcalase as the catalyst are pH 10.0, 35°C, in acetonitrile/Na2CO3-NaHCO3 buffer system (9:1, V/V), reaction time 5 h, with a yield of 63%. The dipeptde product was confirmed by LC- MS. 相似文献
94.
Jin-Mei Xue Yun-Fang An Li-Min Suo Li-Hua Mo Gui Yang Xiang-Qian Luo Da-Bo Liu Chang-Qing Zhao Ping-Chang Yang 《International journal of biological sciences》2021,17(8):2089
Rationale: Corticosteroid resistance (CR) seriously affects the therapeutic effects of steroids on many chronic inflammatory disorders, including airway allergy. The mechanism of CR development is unclear. Recent research indicates that livin, an apoptosis inhibitor, is associated with the regulation in cell activities. This study investigates the role of livin in the inducing and sustaining CR in the airway mucosa.Methods: Nasal epithelial cells (NECs) were isolated from surgically removed nasal mucosal tissues of patients with allergic rhinitis (AR) and nasal polyps with or without CR. Differentially expressed genes in NECs were analyzed by the RNA sequencing. A CR mouse model was developed to test the role of livin in CR development.Results: The results showed that NECs of AR patients with CR expressed high levels of livin, that was positively correlated with the thymic stromal lymphopoietin (TSLP) expression and the high Ras activation status in NECs. Livin and Ras activation mutually potentiating each other in the inducing and sustaining the TSLP expression in NECs. TSLP induced eosinophils and neutrophils to express glucocorticoid receptor-β (GRβ). Eosinophils and neutrophils with high CRβ expression were resistant to corticosteroids. Depletion of livin or inhibition of TSLP markedly attenuated CR and airway allergy.Conclusions: Livin facilitates CR development in the airways by promoting TSLP expression in epithelial cells and the GRβ expression in eosinophils and neutrophils. Depletion of livin or inhibiting TSLP attenuates CR development and inhibits airway allergy, this has the translational potential to be used in the treatment of airway allergy. 相似文献
95.
Sulfolobus solfataricus DNA polymerase IV (Dpo4), a prototype Y-family DNA polymerase, contains a unique little finger domain besides a catalytic
core. Here, we report the chemical shift assignments for the backbone nitrogens, α and β carbons, and amide protons of the
little finger domain of Dpo4. This work and our published backbone assignment for the catalytic core provide the basis for
investigating the conformational dynamics of Dpo4 during catalysis using solution NMR spectroscopy. 相似文献
96.
Guangwen Yin Mei Qin Xianyong Liu Jingxia Suo Xinming Tang Geru Tao Qian Han Xun Suo Wenxue Wu 《Biochemical and biophysical research communications》2013
Immune mapped protein-1 (IMP1) is a new protective protein in apicomplexan parasites, and exits in Eimeria tenella. But its structure and immunogenicity in E. tenella are still unknown. In this study, IMPI in E. tenella was predicted to be a membrane protein. To evaluate immunogenicity of IMPI in E. tenella, a chimeric subunit vaccine consisting of E. tenella IMP1 (EtIMP1) and a molecular adjuvant (a truncated flagellin, FliC) was constructed and over-expressed in Escherichia coli and its efficacy against E. tenella infection was evaluated. Three-week-old AA broiler chickens were vaccinated with the recombinant EtIMP1-truncated FliC without adjuvant or EtIMP1 with Freund’s Complete Adjuvant. Immunization of chickens with the recombinant EtIMP1-truncated FliC fusion protein resulted in stronger cellular immune responses than immunization with only recombinant EtIMP1 with adjuvant. The clinical effect of the EtIMP1-truncated FliC without adjuvant was also greater than that of the EtIMP1 with adjuvant, which was evidenced by the differences between the two groups in body weight gain, oocyst output and caecal lesions of E. tenella-challenged chickens. The results suggested that the EtIMP1-flagellin fusion protein can be used as an effective immunogen in the development of subunit vaccines against Eimeria infection. This is the first demonstration of antigen-specific protective immunity against avian coccidiosis using a recombinant flagellin as an apicomplexan parasite vaccine adjuvant in chickens. 相似文献
97.
Mohammed Freewan Martin D. Rees Tito S. Sempértegui Plaza Elias Glaros Yean J. Lim Xiao Suo Wang Amanda W. S. Yeung Paul K. Witting Andrew C. Terentis Shane R. Thomas 《The Journal of biological chemistry》2013,288(3):1548-1567
The heme enzyme indoleamine 2,3-dioxygenase (IDO) is a key regulator of immune responses
through catalyzing l-tryptophan (l-Trp) oxidation. Here, we show that
hydrogen peroxide (H2O2) activates the peroxidase function of IDO to
induce protein oxidation and inhibit dioxygenase activity. Exposure of IDO-expressing
cells or recombinant human IDO (rIDO) to H2O2 inhibited dioxygenase
activity in a manner abrogated by l-Trp. Dioxygenase inhibition correlated with
IDO-catalyzed H2O2 consumption, compound I-mediated formation of
protein-centered radicals, altered protein secondary structure, and opening of the distal
heme pocket to promote nonproductive substrate binding; these changes were inhibited by
l-Trp, the heme ligand cyanide, or free radical scavengers. Protection by
l-Trp coincided with its oxidation into oxindolylalanine and kynurenine and the
formation of a compound II-type ferryl-oxo heme. Physiological peroxidase substrates,
ascorbate or tyrosine, enhanced rIDO-mediated H2O2 consumption and
attenuated H2O2-induced protein oxidation and dioxygenase
inhibition. In the presence of H2O2, rIDO catalytically consumed
nitric oxide (NO) and utilized nitrite to promote 3-nitrotyrosine formation on IDO. The
promotion of H2O2 consumption by peroxidase substrates, NO
consumption, and IDO nitration was inhibited by l-Trp. This study identifies IDO
as a heme peroxidase that, in the absence of substrates, self-inactivates dioxygenase
activity via compound I-initiated protein oxidation. l-Trp protects against
dioxygenase inactivation by reacting with compound I and retarding compound II reduction
to suppress peroxidase turnover. Peroxidase-mediated dioxygenase inactivation, NO
consumption, or protein nitration may modulate the biological actions of IDO expressed in
inflammatory tissues where the levels of H2O2 and NO are elevated
and l-Trp is low. 相似文献
98.
Jun-Xue Jin Suo LiQing-Shan Gao Yu HongLong Jin Hai-Ying ZhuChang-Guo Yan Jin-Dan Kang Xi-Jun Yin 《Theriogenology》2013
The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) associates with epigenetic aberrancy, including the abnormal acetylation of histones. Altering the epigenetic status by histone deacetylase inhibitors (HDACi) enhances the developmental potential of SCNT embryos. In the current study, we examined the effects of LBH589 (panobinostat), a novel broad-spectrum HDACi, on the nuclear reprogramming and development of pig SCNT embryos in vitro. In experiment 1, we compared the in vitro developmental competence of nuclear transfer embryos treated with different concentrations of LBH589. Embryos treated with 50 nM LBH589 for 24 hours showed a significant increase in the rate of blastocyst formation compared with the control or embryos treated with 5 or 500 nM LBH589 (32.4% vs. 11.8%, 12.1%, and 10.0%, respectively, P < 0.05). In experiment 2, we examined the in vitro developmental competence of nuclear transfer embryos treated with 50 nM LBH589 for various intervals after activation and 6-dimethylaminopurine. Embryos treated for 24 hours had higher rates of blastocyst formation than the other groups. In experiment 3, when the acetylation of H4K12 was examined in SCNT embryos treated for 6 hours with 50 nM LBH589 by immunohistochemistry, the staining intensities of these proteins in LBH589-treated SCNT embryos were significantly higher than in the control. In experiment 4, LBH589-treated nuclear transfer and control embryos were transferred into surrogate mothers, resulting in three (100%) and two (66.7%) pregnancies, respectively. In conclusion, LBH589 enhances the nuclear reprogramming and developmental potential of SCNT embryos by altering the epigenetic status and expression, and increasing blastocyst quality. 相似文献
99.
The secretory pathway is responsible for the transport of newly synthesized transmembrane proteins from the endoplasmic reticulum to their destinations via the Golgi/trans-Golgi network (TGN), Cargo proteins at each sta- tion are actively sorted by specific sorting signals on the cargo and the corresponding coat complexes. Here, we used the Arabidopsis regulator of G-protein signaling (AtRGS1), which contains an N-terminal potentially sensing glucose seven-transmembrane domain and a C-terminal RGS domain, as a model to uncover sorting motifs required for its cell surface expression. Expression of wild-type and truncated or mutated AtRGS1 fluorescent fusion proteins identified two cysteine residues in the extracellular N-terminus that are essential for endoplasmic reticulum exit and/or correct folding of AtRGS1. The linker between the seven-transmembrane and RGS domains contains an endoplasmic reticulum export signal, whereas the C-terminus is dispensable for the plasma membrane expression of AtRGS1. Interestingly, deletion of the RGS domain results in Golgi/TGN localization of the truncated AtRGS1. Further analysis using site-directed mutagen- esis showed that a tyrosine-based motif embedded in the RGS domain is essential for Golgi/TGN export of AtRGS1. These results reveal a new role for the RGS domain in regulating AtRGS1 trafficking from the Golgi/TGN to the plasma membrane and explain the interaction between the seven-transmembrane and RGS domains. 相似文献
100.
To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2'-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the "steric gate", establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review. 相似文献