Changsha, China
Changsha, China

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Zhao L.,Peking University | Xu J.,Mawangdui Hospital | Wang Q.,Peking University | Feng W.,Peking University | And 2 more authors.
Brain Research | Year: 2015

In recent years, GLP-1 and its analogs have been developed for the treatment of type 2 diabetes. It has been reported that stimulating the GLP-1 receptor can protect neurons against metabolic and oxidative insults, and therefore can be used in the treatment of stroke and Parkinson's disease. The present study aimed to examine the neuroprotective effects of rhGLP-1 (7-36) and its possible mechanisms against acute ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in diabetic rats. The type 2 diabetic rat model was established by a combination of a high-fat diet and low-dose streptozotocin (STZ). RhGLP-1 (7-36) (20, 40, 80 μg/kg) was given intraperitoneally before reperfusion. The neuroprotective effects of rhGLP-1 (7-36) were evaluated by changes in neurological deficit scores and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Changes in blood glucose were used to assess hypoglycemic effects. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), inducible nitric oxide syntheses (iNOS) and endothelial nitric oxide syntheses (eNOS) after MCAO/R administration (2 h and 46 h) were examined to investigate the possible mechanisms of RhGLP-1 (7-36). Haematoxylin and eosin (H&E) staining was used for histopathological observation. Compared with the control group, rhGLP-1 (7-36)-treated groups decreased nerve function deficiency scores; significantly reduced infarction volume percentage, MDA, iNOS and blood glucose; and significantly increased SOD, GSH-PX and eNOS. In addition, rhGLP-1 (7-36) groups enhanced the density of surviving neurons and increased vascular proliferation. The current study suggests a neuroprotective effect of rhGLP-1 (7-36) in diabetic MCAO/R rats since anti-oxidative and anti-nitrosative stress effects can contribute to beneficial effects against ischemia/reperfusion injury. © 2015 Elsevier B.V. All rights reserved.


Xu J.,Mawangdui Hospital | Qian Z.,The First Hospital | Zhao L.,Peking University | Fang Y.,Peking University
Biomedical Chromatography | Year: 2014

An optimized HPLC/MS/MS method was established to quantify glutamate (Glu) and aspartic acid (Asp) in rat hippocampus with glutamate-d5 (Glu-d5) as internal standard. The mass spectrometry was operated under the multiple reaction monitoring mode using electrospray ionization in the positive ion mode for Glu and negative ion mode for Asp. The retention times of Glu, Asp and Glu-d5 were 1.53, 2.07 and 1.52min, respectively. The linearity of calibration curves was good, with r2>0.99 and a lower limit of quantitation of 10ng/mL. The intra-day precisions (relative standard deviation, RSD) of Glu and Asp were in the range of 3.61-8.17 and 4.22-10.09%, respectively; the inter-day precisions (RSD) of Glu and Asp were in the range of 3.57-5.19 and 2.49-5.04%, respectively. The accuracies of Glu and Asp were in the range of -2.10-6.20 and -0.90-10.00%, respectively. The recovery rates of 10, 100 and 1000ng/mL were found to be 0.89±0.24, 1.01±0.10 and 0.90±0.12 for Glu and 0.99±0.26, 0.93±0.07 and 1.13±0.13 for Asp, respectively. This optimized method was successfully applied to quantify the concentration of Glu and Asp in rat hippocampus in brain ischemia/reperfusion research. © 2014 John Wiley & Sons, Ltd.


Liu M.-H.,University of South China | Zhang Y.,Mawangdui Hospital | He J.,University of South China | Tan T.-P.,University of South China | And 6 more authors.
International Journal of Molecular Medicine | Year: 2016

Doxorubicin (DOX) is an efficient drug used in cancer therapy that also produces reactive oxygen species (ROS) that induces severe cytotoxicity, which limits its clinical application. Hydrogen sulfide (H2S), a novel gasotransmitter, has been shown to exert cardioprotective effects. The present study aimed to determine whether exogenous H2S protects H9c2 cardiac cells against DOX-induced cytotoxicity and whether these protective effects are mediated through the PI3K/Akt/FoxO3a pathway. The H9c2 cardiac cells were exposed to 5 M DOX for 24 h to establish a model of DOX-induced cardiotoxicity. The results showed that the treatment of H9c2 cardiac cells with sodium hydrosulfi de (NaHS) for 30 min prior to DOX exposure markedly attenuated the phosphorylation of Akt and FoxO3a. Notably, pre-treatment of the H9c2 cells with NaHS significantly attenuated the nuclear localization of FoxO3a as well as the apoptosis of H9c2 cells induced by DOX. The treatment of H9c2 cells with N-acetyl-L-cysteine (NAC), a scavenger of ROS, prior to DOX exposure, also markedly increased the phosphorylation of Akt and FoxO3a which was inhibited by DOX alone. Furthermore, pre-treatment with LY294002, a selective inhibitor of PI3K/Akt, reversed the protective effect of H2S against DOX-induced injury of cardiomyocytes, as demonstrated by an increased number of apoptotic cells, a decrease in cell viability and the reduced phosphorylation of Akt and FoxO3a. These fi ndings suggested that exogenous H2S attenuates DOX-induced cytotoxic effects in H9c2 cardiac cells through the PI3K/Akt/FoxO3a pathway.


Liu M.-H.,University of South China | Shan J.,Zhongshan Torch Development Zone Hospital | Li J.,BoAi Hospital of Zhongshan | Zhang Y.,Mawangdui Hospital | Lin X.-L.,Huizhou University
Experimental and Therapeutic Medicine | Year: 2016

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it can induce severe cytotoxicity, which limits its clinical application. In the present study, the effects of resveratrol (RES) on sirtuin 1 (SIRT1) activation in mediating DOX-induced cytotoxicity in H9c2 cardiac cells was investigated. H9c2 cells were exposed to 5 μM DOX for 24 h to establish a model of DOX cardiotoxicity. Apoptosis of H9c2 cardiomyocytes was assessed using the MTT assay and Hoechst nuclear staining. The results demonstrated that pretreating H9c2 cells with RES prior to the exposure of DOX resulted in increased cell viability and a decreased quantity of apoptotic cells. Western blot analysis demonstrated that DOX decreased the expression level of SIRT1. These effects were significantly alleviated by co-treatment with RES. In addition, the results demonstrated that DOX administration amplified forkhead box O1 (FoxO1) and P53 expression levels in H9c2 cells. RES was also found to protect against DOX-induced increases of FoxO1 and P53 expression levels in H9c2 cells. Furthermore, the protective effects of RES were arrested by the SIRT1 inhibitor nicotinamide. In conclusion, the results demonstrated that RES protected H9c2 cells against DOX-induced injuries via SIRT1 activation. © 2016, Spandidos Publications. All rights reserved.


Liu M.-H.,University of South China | Yuan C.,The First Hospital of Changsha | He J.,University of South China | Tan T.-P.,University of South China | And 10 more authors.
Cellular and Molecular Neurobiology | Year: 2015

Diabetes is known to be associated with neurodegenerative diseases. Resveratrol, a plant-derived polyphenolic compound found in red wine, possesses antioxidant properties. In this study, we aimed to investigate the effects of resveratrol on the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway in mediating high glucose (HG)-induced injuries in neuronal PC12 cells. PC12 cells were exposed to HG to establish a model of HG neurotoxicity. Results showed that pre-treating PC12 cells with resveratrol before exposure to HG led to increased cell viability, decreased apoptotic cells, and reactive oxygen species generation. Western blot analysis showed that HG decreased the phosphorylation of Akt and FoxO3a and led to the nuclear localization of FoxO3a. These effects were significantly alleviated by resveratrol co-treatment. Furthermore, the protective effects of resveratrol were abolished by PI3K/Akt inhibitor LY294002. All these results demonstrate that resveratrol protected the PC12 cells from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway. © 2014, Springer Science+Business Media New York.


PubMed | Boai Hospital of Zhongshan, Huizhou University, University of South China, Mawangdui Hospital and The First Hospital of Changsha
Type: Journal Article | Journal: Molecular medicine reports | Year: 2015

Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOXinduced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOXinduced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOXinduced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with NacetylLcysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOXinduced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine--lyase were examined by western blotting.


PubMed | University of South China and Mawangdui Hospital
Type: Journal Article | Journal: International journal of molecular medicine | Year: 2016

Doxorubicin(DOX) is an efficient drug used in cancer therapy that also produces reactive oxygen species(ROS) that induces severe cytotoxicity, which limits its clinical application. Hydrogen sulfide(H2S), a novel gasotransmitter, has been shown to exert cardioprotective effects. The present study aimed to determine whether exogenous H2S protects H9c2 cardiac cells against DOX-induced cytotoxicity and whether these protective effects are mediated through the PI3K/Akt/FoxO3a pathway. The H9c2 cardiac cells were exposed to 5M DOX for 24h to establish a model of DOX-induced cardiotoxicity. The results showed that the treatment of H9c2 cardiac cells with sodium hydrosulde(NaHS) for 30min prior to DOX exposure markedly attenuated the phosphorylation of Akt and FoxO3a. Notably, pre-treatment of the H9c2 cells with NaHS significantly attenuated the nuclear localization of FoxO3a as well as the apoptosis of H9c2 cells induced by DOX. The treatment of H9c2 cells with N-acetyl-L-cysteine(NAC), a scavenger of ROS, prior to DOX exposure, also markedly increased the phosphorylation of Akt and FoxO3a which was inhibited by DOX alone. Furthermore, pre-treatment with LY294002, a selective inhibitor of PI3K/Akt, reversed the protective effect of H2S against DOX-induced injury of cardiomyocytes, as demonstrated by an increased number of apoptotic cells, a decrease in cell viability and the reduced phosphorylation of Akt and FoxO3a. These ndings suggested that exogenous H2S attenuates DOX-induced cytotoxic effects in H9c2 cardiac cells through the PI3K/Akt/FoxO3a pathway.


PubMed | Boai Hospital of Zhongshan, The Third Peoples Hospital of Huizhou, University of South China, Mawangdui Hospital and The First Hospital of Changsha
Type: Journal Article | Journal: Molecular medicine reports | Year: 2015

Doxorubicin (DOX) is a potent and available antitumor therapeutic agent; however, its clinical application is limited due to its cardiotoxicity. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOXinduced cardiotoxicity. Therefore, the aim of the present study was to investigate whether the extracellular signalregulated kinase (ERK) 1/2 signaling pathway is involved in the cardioprotection of H2S against DOXinduced cardiotoxicity. The present study demonstrated that pretreatment with sodium hydrosulde (NaHS; a donor of H2S) prior to DOX exposure attenuated the decreased cell viability, the increased apoptosis rate and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cardiac myocytes. Exposure of H9c2 cardiac myocytes to DOX upregulated the expression levels of phosphorylated ERK1/2, which had been reduced by pretreatment with NaHS or NacetylLcysteine, a ROS scavenger. In addition, H2S upregulated the antiapoptotic protein, Bcl2 and downregulated the proapoptotic protein, Bax. Notably, U0126, a selective inhibitor of ERK1/2, was observed to mimic the abovementioned cytoprotective activity of H2S. In conclusion, these findings indicate that H2S attenuates DOXinduced cardiotoxicity by inhibiting ROS-mediated activation of ERK1/2 in H9c2 cardiac myocytes.


PubMed | BoAi Hospital of Zhongshan, Huizhou University, University of South China, Mawangdui Hospital and The First Hospital of Changsha
Type: Journal Article | Journal: Molecular medicine reports | Year: 2016

Resveratrol is a polyphenolic compound found in wine, which is mainly produced by the grapevine and exerts chemopreventive effects against hepatocellular carcinoma. However, the underlying molecular mechanisms have remained to be fully elucidated. The present study assessed whether resveratrol-induced apoptosis was mediated via the activation of the forkhead box O3a (FoxO3a) transcription factor. It was demonstrated that resveratrol treatment induced apoptosis in HepG2 cells, and that this pro-apoptotic effect was accompanied with increases in the expression of apoptotic protein Bim. Following resveratrol treatment, Akt-mediated phosphorylation of FoxO3a was observed to be diminished in HepG2 cells. Furthermore, resveratrol enhanced the nuclear levels of FoxO3a and mediated neuronal death via Bim. The present study demonstrated that resveratrol induced apoptosis in HepG2 cells through activation of the transcription factor FoxO3a and increasing the expression of Bim protein.


Xie W.,Central South University | Xie W.,Mawangdui Hospital | Xie H.,Central South University | Liu F.,Central South University | And 7 more authors.
British Journal of Dermatology | Year: 2013

Background Infantile haemangiomas (IHs) are benign tumours in infancy. Most patients suffering from IHs do not require treatment. However, if there is a dramatic aesthetic or functional impairment, treatment is needed. Currently the most promising therapy for complicated IHs is the oral administration of propranolol, but its mechanism is unclear. Objectives To investigate the role of CD147 in propranolol-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Methods Human umbilical vein endothelial cells were treated with propranolol, and the treatment effects were investigated through the following methodology. (i) Cell proliferation and apoptosis were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis. (ii) The expression level of CD147 was measured by reverse-transcription polymerase chain reaction and Western blotting. (iii) HUVECs were transfected with lentivirus encoding CD147 short hairpin (sh)RNA or CD147 cDNA. Ensuing changes in cell proliferation and apoptosis after transfection were measured using the MTT assay and flow cytometry. (iv) The level of phosphorylation of Bcl-2-associated death promoter (BAD) at Ser112 in HUVECs after propranolol treatment and/or CD147 shRNA transfection was detected by Western blotting. Results Propranolol inhibited cell proliferation and induced apoptosis in HUVECs. It decreased CD147 protein expression in a concentration-dependent manner. Knocking down CD147 not only induced apoptosis but also exacerbated the apoptosis triggered by propranolol in HUVECs. Overexpression of CD147 can protect HUVECs from apoptosis and propranolol-induced apoptosis. Furthermore, knockdown of both propranolol and CD147 can downregulate Ser112 phosphorylation of BAD, indicating that propranolol and CD147 induce apoptosis in HUVECs through the same signalling transduction pathway. Conclusions Our studies demonstrate that propranolol-induced apoptosis may be mediated through the downregulation of CD147 in HUVECs. This study highlights a novel step in propranolol action and suggests a potential new target for the treatment of IHs. © 2013 The Authors. BJD © 2013 British Association of Dermatologists.

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