Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica

Wuhan, China

Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica

Wuhan, China
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Liu H.,Huazhong University of Science and Technology | Liu H.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | Xu H.,Huazhong University of Science and Technology | Xu H.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | And 2 more authors.
Metallomics | Year: 2017

Atherosclerosis and related cardiovascular diseases (CVDs) represent the greatest threats to human health worldwide. Selenium, an essential trace element, is incorporated into selenoproteins that play a crucial role in human health and disease. Although findings from a limited number of randomized trials have been inconsistent and cannot support a protective role of Se supplementation in CVDs, prospective observational studies have generally shown a significant inverse association between selenium or selenoprotein status and CVD risk. Furthermore, a benefit of selenium supplementation in the prevention of CVDs has been seen in population with low baseline selenium status. Evidence from animal studies shows consistent results that selenium and selenoproteins might prevent experimental atherosclerosis, which can be explained by the molecular and cellular effects of selenium observed both in animal models and cell cultures. Selenoproteins of particular relevance to atherosclerosis are glutathione peroxidases, thioredoxin reductase 1, selenoprotein P, selenoprotein S. The present review is focusing on the existing evidence that supports the concept that optimal selenium intake can prevent atherosclerosis. Its underlying mechanisms include inhibiting oxidative stress, modulating inflammation, suppressing endothelial dysfunction, and protecting vascular cells against apoptosis and calcification. However, the benefit of selenium supplementation in the prevention of atherosclerosis remains insufficiently documented so far. Future studies with regard to the effects of selenium supplementation on atherosclerosis should consider many factors, especially the baseline selenium status, the dose and forms of selenium supplementation, and the selenoprotein genotype. Additionally, much more studies are needed to confirm the roles of selenoproteins in atherosclerosis prevention and clarify the underlying mechanisms. © The Royal Society of Chemistry.


Zhao J.,Wuhan University of Science and Technology | Wu J.,Wuhan University of Science and Technology | Yang Z.,University of Houston | Li H.,Wuhan University of Science and Technology | And 3 more authors.
Chemical Research in Toxicology | Year: 2017

Amyloid-β plaques and oxidative stress are the major hallmarks of Alzheimer’s disease. Our previous study found that the heme-Aβ complex enhanced the catalytic effect of free heme on protein tyrosine nitration in the presence of hydrogen peroxide (H2O2) and nitrite (NO2 -). Y10 in Aβ could be the first target to be nitrated. We also found that nitration of Aβ1-40 significantly decreased its aggregation. However, a contrary report showed that nitration of Aβ1-42 by peroxynitrite enhanced its aggregation. To rule out the interference of peroxynitrite caused Aβ oxidation, we used synthetic Y10 nitrated Aβ1-42 to study the influence of Y10 nitration on Aβ1-42’s aggregation and cytotoxicity in this study. We confirmed that Aβ1-42 could be nitrated in the presence of H2O2, NO2 -, and heme by dot blotting. CD spectroscopy showed an increase of β-sheet structure of Aβ1-42 and its mutants. The thioflavin T (ThT) flourescence assay revealed that both nitration and chlorination significantly inhibited Aβ1-42 fibril formation. TEM and AFM observations of Aβ peptide aggregates further confirmed that Y10 modification inhibited Aβ1-42 fibril formation. The cytotoxicity study of native and modified Aβ peptides on SH-SY5Y cells revealed that nitration of Aβ1-42 remarkably decreased the neurotoxicity of Aβ1-42. On the basis of these results, we hypothesized that nitration of Y10 may block the π-π stacking interactions of Aβ1-42 so that it inhibit its aggregation and neurotoxicity. More importantly, considerable evidence suggested that the levels of nitrite plus nitrate significantly decreased in the brain of AD patients. Thus, we believe that these findings would be helpful for further understanding the function of Aβ in AD. © 2017 American Chemical Society.


Zhang Y.,Huazhong University of Science and Technology | Zhang Y.,Xihua University | Huang Y.,Huazhong University of Science and Technology | Deng X.,Nanchang University | And 4 more authors.
European Journal of Pharmacology | Year: 2012

Baicalin has been reported to protect against liver injury in iron-overload mice, however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In this study, we systematically studied the protective effect of baicalin on iron overload induced liver injury, as well as the underlying mechanism based on nitrative stress in rat model. We found that when iron overload rats (500 mg iron/kg) were fed baicalin-containing diet (0.3% and 1% w/w) for 45 days, baicalin dose dependently protected against iron overload induced liver injury, including alleviation of hepatic pathological damage, decrease of SOD activity, iron content, carbonyl content, and the thiobarbituric acid-reactive substances level in hepatic tissues. It also increased serum iron content, SH content and GPx activity, decreased serum ALT and AST activities. Immunohistochemistry and immunoprecipitation analysis revealed that baicalin could also inhibit iron overload induced protein tyrosine nitration in liver. Moreover, in iron overload rat liver, we found that baicalin decreased the iron overload increased level of glutathione-S- transferases (GSTs) expression, oxidation and nitration. These results suggest that not only oxidative stress, but also nitrative stress, is involved in iron overload induced liver injury, and the underlying mechanism might partially relate to the involvement of GSTs expression and post-translational modification. Baicalin can effectively prevent iron overload caused abnormality and can be a candidate medicine for iron overload diseases. © 2012 Elsevier B.V. All rights reserved.


Ye H.,Huazhong University of Science and Technology | Ye H.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | Yang Z.,University of Houston | Li H.,Huazhong University of Science and Technology | And 3 more authors.
Dalton Transactions | Year: 2017

Neuropeptide Y (NPY) is a member of the pancreatic peptide family of neuropeptides that play a crucial role in numerous central and peripheral nervous system responses. Recently, it has been shown that NPY protects cells against neurotoxic damage from β-amyloid peptides (Aβ) in Alzheimer's disease (AD). Heme is a common factor linking several metabolic perturbations in AD and altered heme metabolism has been shown to be related to the pathologies of AD. Thus, heme may have a chance to act on NPY and potentially counteract its function. To explore this, UV-visible spectroscopy, fluorescence spectroscopy and differential pulse voltammetry (DPV) were used to demonstrate that NPY can bind with heme to form a NPY-heme complex and the binding enhances the peroxidase activity of heme. Dot blotting results indicate that NPY is easily nitrated upon binding with heme when H2O2 and NO2 - are present. Furthermore, LC-MS/MS results confirm that tyrosine36 (Tyr36), an important amino acid residue of NPY in binding and activating neuropeptide receptors, can be nitrated during the nitration process. Thereafter, we used mutant peptide NPY(3N) (Tyr36 replaced by 3-nitrotyrosine) to investigate the impact of nitration on the structure and bioactivity of the peptide. Our results show that Tyr36 nitration destabilizes the α-helix conformation of the peptide, and counteracts NPY-induced inhibition of cAMP accumulation in SK-N-MC cells. Collectively, these data imply that the self-association of NPY with heme potentially induces tyrosine nitration, destroys the active monomeric conformation of the peptide and thereby counteracts its bioactivity. © 2017 The Royal Society of Chemistry.


Lu N.,Jiangxi Normal University | Lu N.,Huazhong University of Science and Technology | Yi L.,Huazhong University of Science and Technology | Deng Q.,Huazhong University of Science and Technology | And 5 more authors.
Toxicology in Vitro | Year: 2012

Our previous research demonstrated that iron chelating agent desferrioxamine (DFO) could promote iron donor hemin-induced protein oxidation due to the combination of DFO and hemin, but the binding constant and thermodynamic parameters of DFO-hemin interaction have not been examined before. In this study, affinity capillary electrophoresis (ACE) was applied to investigate the interaction between DFO and hemin for the first time. The binding constants of DFO-hemin were calculated to be 10 4-10 5M -1 at various temperatures. The negative value of various thermodynamic parameters (ΔG, ΔS, and ΔH) suggested that the binding was spontaneous and the interaction was exothermic and entropically driven. In addition, the high binding affinity between DFO with hemin seemed to be the key factor on promoting hemin- catalyzed formation of cytotoxic radicals, such as superoxide (O2-), which was related to the potential toxicity of this drug in clinical use. © 2012 Elsevier Ltd.


Li X.,Huazhong University of Science and Technology | Li X.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | Li H.,Huazhong University of Science and Technology | Li H.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | And 7 more authors.
Biochimie | Year: 2012

Excessive tissue iron levels are associated with the increase of oxidative/nitrative stress which contributes to tissue damage that may elevate the risk of diabetes. Therefore, we investigated the effects of iron on diabetes-associated liver injury and whether iron-related tyrosine nitration participated in this process. Rats were randomly divided into four groups: control, iron overload (300 mg/kg iron dextran, i.p.), diabetic (35 mg/kg of streptozotocin i.p. after administration of a high-fat diet) and diabetic simultaneously treated with iron. Iron supplement markedly increased diabetes-mediated liver damage and hepatic dysfunction by increasing liver/body weight ratio, serum levels of aspartate and alanine aminotransferase, and histological examination, which were correlated with elevated levels of lipid peroxidation, protein carbonyls and tyrosine nitration, oxidative metabolism of nitric oxide, and reduced antioxidant capacity. Consequently, the extent of oxidized/nitrated glucokinase was markedly increased in the iron-treated diabetic rats that contribute to a decrease in its expression and activity. Further studies revealed a significant contribution of iron-induced specific glucokinase nitration sites to its inactivation. In conclusion, iron facilitates diabetes-mediated elevation of oxidative/nitrative stress, simultaneously impairs liver GK, and can be a link between enzymatic changes and hepatic dysfunction. These findings may provide new insight on the role of iron in the pathogenesis of diabetes mellitus. © 2012 Elsevier Masson SAS. All rights reserved.


Zhao J.,Huazhong University of Science and Technology | Zhao J.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | Wang P.,Huazhong University of Science and Technology | Wang P.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | And 4 more authors.
Chemical Research in Toxicology | Year: 2015

Amyloid β peptide (Aβ) aggregation is considered to be a crucial pathological biomarker of Alzheimers disease (AD). It was found that Aβ and heme can form an Aβ-heme complex, which results in increased heme pseudoperoxidase activity. Recently, we found that increasing pseudoperoxidase activity induces elevated tyrosine nitration on Aβ in the presence of nitrite and hydrogen peroxide. However, the nature of tyrosine nitration of Aβ and its physiologic significance are still unknown. In this study, we revealed that Aβ1-40 can be nitrated in vitro by binding to heme in the presence of nitrite and hydrogen peroxide. Moreover, we found that tyrosine nitration had little effect on Aβ1-40s binding activity with heme. A TMB assay also revealed that the peroxidase activity of the heme-Aβ1-40Y10(3N)T (tyrosine 10 was replaced with 3-nitrtotyrosine in Aβ1-40) complex was moderately increased compared with that of the heme-Aβ1-40 complex. Furthermore, Thioflavin T fluorescence and transmission electron microscopic characterization indicated that tyrosine nitration significantly decreased the aggregation of Aβ1-40. In addition, a cytotoxicity test verified that wild-type Aβ1-40 was more cytotoxic than that of Aβ1-40Y10(3N)T. These results suggest that nitration of Aβ1-40 might be an Aβ detoxicant process and a compensatory reaction to nitrative stress. Our findings may lead to a detailed understanding of the function of Aβ1-40 and may be helpful in preventing and curing AD. © 2014 American Chemical Society.


Yuan C.,Huazhong University of Science and Technology | Yuan C.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | Yi L.,Huazhong University of Science and Technology | Yi L.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | And 10 more authors.
Journal of Biological Inorganic Chemistry | Year: 2012

Amyloid beta (Aβ) peptide accumulation has been demonstrated to play a central role in Alzheimer's disease (AD). Substantial evidence indicates that protein nitrotyrosination contributes to Aβ-dependent neurotoxicity; however, the molecular mechanism is unknown. Recent research has shown that Aβ complexes with heme to form Aβ-heme, and increases the pseudo-peroxidase activity of heme. We found that Aβ-heme uses H #2O 2 and NO 2 - to cause nitration of enolase and synaptic proteins more effectively than heme. Thus, the increased peroxidase activity of Aβ-heme may be the molecular link between excess Aβ and the widespread protein nitration in AD. Interestingly, the site of enolase nitration that was catalyzed by Aβ-heme is different from that induced by heme. Moreover, the secondary structural perturbations of Aβ-heme-treated and heme-treated enolase are also different. These observations suggest that Aβ-heme targets specific amino acid sequences in enolase. Furthermore, our data show that Aβ-heme peroxidase activity is independent of the aggregation state of Aβ, suggesting an important role of soluble Aβ in addition to Aβ aggregates and oligomers in AD pathogenesis. © SBIC 2011.


Liu H.,Huazhong University of Science and Technology | Liu H.,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica | Bian W.,Huazhong University of Science and Technology | Liu S.,Huazhong University of Science and Technology | And 2 more authors.
Biological Trace Element Research | Year: 2012

Osteoporosis is a bone disease that leads to an increased risk of fracture. Oxidative stress may play a major role in the development of osteoporosis in part by inhibiting osteoblastic differentiation of bone marrow stromal cells (MSCs). Some evidence suggested that antioxidant selenium could prevent osteoporosis, but the underlying mechanism remains unclear. In this work, the effect of sodium selenite on H2O2-induced inhibition of osteoblastic differentiation of primary rat bone MSCs and the related mechanisms were examined. Pretreatment with selenite inhibited the adverse effect of H2O2 on osteoblastic differentiation of MSCs, based on alkaline phosphatase activity, gene expression of type I collagen and osteocalcin, and matrix mineralization. In addition, selenite pretreatment also suppressed the activation of extracellular signal-regulated kinase (ERK) induced by H2O2. The above effects were mediated by the antioxidant effect of selenite. Selenite enhanced the gene expression and activity of glutathione peroxidase, reversed the decreased total antioxidant capacity and reduced glutathione, and suppressed reactive oxygen species production and lipid peroxidation level in H2O2-treated MSCs. These results showed that selenite protected MSCs against H 2O2-induced inhibition of osteoblastic differentiation through inhibiting oxidative stress and ERK activation, which provided, for the first time, the mechanistic explanation for the negative association of selenium status and risk of osteoporosis in terms of bone formation. © 2012 Springer Science+Business Media, LLC.


Ye Y.,Huazhong University of Science and Technology | Fu F.,Huazhong University of Science and Technology | Li X.,Huazhong University of Science and Technology | Yang J.,Huazhong University of Science and Technology | And 2 more authors.
Journal of Cellular Biochemistry | Year: 2016

Atherosclerosis and related cardiovascular diseases (CVD) represent one of the greatest threats to human health worldwide. The protection of vascular smooth muscle cells (VSMCs) from apoptosis in the plaque has become an important therapeutic target for atherosclerotic plaque stabilization. A significant association of selenoprotein S (SelS) gene polymorphism with atherosclerotic CVD has been reported in epidemiologic studies, but the underlying mechanism remains unknown. In this paper, SelS expression in the thoracic aorta and its role in the protection of VSMCs from apoptosis have been studied. Western blot analysis showed that SelS was highly expressed in rat thoracic aorta. SelS gene silence by small interference RNA (siRNA) rendered VSMCs more sensitive to hydrogen peroxide- or tunicamycin- induced injury and apoptosis, as determined by MTT assay, Hoechst staining, and annexin V/propidium iodide staining. SelS silence aggravated hydrogen peroxide-induced oxidative stress and phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) in VSMCs. Furthermore, SelS silence enhanced endoplasmic reticulum (ER) stress induced by hydrogen peroxide or tunicamycin, as showed by the increased protein levels of ER chaperone 78 kDa glucose-regulated protein (GRP78), ER stress transducer phosphorylated protein kinase RNA like ER kinase (PERK), and the proapoptotic transcription factor C/EBP homologous protein (CHOP). In conclusion, the present study suggested that SelS highly expressed in the blood vessel might protect VSMCs from apoptosis by inhibiting oxidative stress and ER stress. Our finding provided mechanistic insights for the potential preventive role of SelS in atherosclerotic CVD. © 2015 Wiley Periodicals, Inc.

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