Publications by authors named "Guimei Guan"

10 Publications

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HO-1 nuclear accumulation and interaction with NPM1 protect against stress-induced endothelial senescence independent of its enzymatic activity.

Cell Death Dis 2021 Jul 26;12(8):738. Epub 2021 Jul 26.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, China.

Heme oxygenase-1 (HO-1) has attracted accumulating attention for its antioxidant enzymatic activity. However, the exact regulatory role of its non-enzymatic activity in the cardiovascular system remains unaddressed. Here, we show that HO-1 was accumulated in the nuclei of stress-induced senescent endothelial cells, and conferred protection against endothelial senescence independent of its enzymatic activity. Overexpression of ΔHO-1, a truncated HO-1 without transmembrane segment (TMS), inhibited HO-induced endothelial senescence. Overexpression of ΔHO-1, the catalytically inactive form of ΔHO-1, also exhibited anti-senescent effect. In addition, infection of recombinant adenovirus encoding ΔHO-1 with three nuclear localization sequences (NLS), alleviated endothelial senescence induced by knockdown of endogenous HO-1 by CRISPR/Cas9. Moreover, repression of HO-1 nuclear translocation by silencing of signal peptide peptidase (SPP), which is responsible for enzymatic cleavage of the TMS of HO-1, exacerbated endothelial senescence. Mechanistically, nuclear HO-1 interacted with NPM1 N-terminal portion, prevented NPM1 translocation from nucleolus to nucleoplasm, thus disrupted NPM1/p53/MDM2 interactions and inhibited p53 activation by NPM1, finally resisted endothelial senescence. This study provides a novel understanding of HO-1 as a promising therapeutic strategy for vascular senescence-related cardiovascular diseases.
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http://dx.doi.org/10.1038/s41419-021-04035-6DOI Listing
July 2021

Pterostilbene and its nicotinate derivative ameliorated vascular endothelial senescence and elicited endothelium-dependent relaxations via activation of sirtuin 1.

Can J Physiol Pharmacol 2021 Feb 2:1-10. Epub 2021 Feb 2.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences; National and Local United Engineering Lab of Druggability and New Drugs Evaluation; Guangdong Engineering Laboratory of Druggability and New Drug Evaluation; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, P.R. China.

Vascular endothelial cell senescence is a leading cause of age-associated diseases and cardiovascular diseases. Interventions and therapies targeting endothelial cell senescence and dysfunction would have important clinical implications. This study evaluated the effect of 10 resveratrol analogues, including pterostilbene (Pts) and its derivatives, against endothelial senescence and dysfunction. All the tested compounds at the concentrations from 10 M to 10 M did not show cytotoxicity in endothelial cells by MTT assay. Among the 10 resveratrol analogues, Pts and Pts nicotinate attenuated the expression of senescence-associated β-galactosidase, downregulated p21 and p53, and increased the production of nitric oxide (NO) in both angiotensin II - and hydrogen peroxide - induced endothelial senescence models. In addition, Pts and Pts nicotinate elicited endothelium-dependent relaxations, which were attenuated in the presence of endothelial NO synthase (eNOS) inhibitor L-NAME or sirtuin 1 (SIRT1) inhibitor sirtinol. Pts and Pts nicotinate did not alter SIRT1 expression but enhanced its activity. Both Pts and Pts nicotinate have high binding activities with SIRT1, according to surface plasmon resonance results and the molecular docking analysis. Inhibition of SIRT1 by sirtinol reversed the anti-senescent effects of Pts and Pts nicotinate. Moreover, Pts and Pts nicotinate shared similar ADME (absorption, distribution, metabolism, excretion) profiles and physiochemical properties. This study suggests that the Pts and Pts nicotinate ameliorate vascular endothelial senescence and elicit endothelium-dependent relaxations via activation of SIRT1. These two compounds may be potential drugs for the treatment of cardiovascular diseases related to endothelial senescence and dysfunction.
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http://dx.doi.org/10.1139/cjpp-2020-0583DOI Listing
February 2021

Rhamnocitrin extracted from Nervilia fordii inhibited vascular endothelial activation via miR-185/STIM-1/SOCE/NFATc3.

Phytomedicine 2020 Dec 19;79:153350. Epub 2020 Sep 19.

Mathematical Engineering Academy of Chinese Medicine; Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China. Electronic address:

Background: Vascular endothelial activation is pivotal for the pathological development of various infectious and inflammatory diseases. Therapeutic interventions to prevent endothelial activation are of great clinical significance to achieve anti-inflammatory strategy. Previous studies indicate that the total flavonoids from the endemic herbal medicine Nervilia fordii (Hance) Schltr exerts potent anti-inflammatory effect and protective effect against endotoxin lipopolysaccharide (LPS)-induced acute lung injury, and shows clinical benefit in severe acute respiratory syndromes (SARS). However, the exact effective component of Nervilia fordii and its potential mechanism remain unknown.

Purpose: The aim of this study was to investigate the effect and mechanism of rhamnocitrin (RH), a flavonoid extracted from Nervilia fordii, on LPS-induced endothelial activation.

Methods: The in vitro endothelial cell activation model was induced by LPS in human umbilical vein endothelial cells (HUVECs). Cell viability was measured to determine the cytotoxicity of RH. RT-PCR, Western blot, fluorescent probe and immunofluorescence were conducted to evaluate the effect and mechanism of RH against endothelial activation.

Results: RH was extracted and isolated from Nervilia fordii. RH at the concentration from 10 M-10 M inhibited the expressions of interlukin-6 (IL-6) and -8 (IL-8), monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) in response to LPS challenge. Mechanistically, RH repressed calcium store-operated Ca entry (SOCE) induced by LPS, which is due to downregulation of stromal interaction molecule-1 (STIM-1) following upregulating microRNA-185 (miR-185). Ultimately, RH abrogated LPS-induced activation of SOCE-mediated calcineurin/NFATc3 (nuclear factor of activated T cells, cytoplasmic 3) signaling pathway.

Conclusion: The present study identifies RH as a potent inhibitor of endothelial activation. Since vascular endothelial activation is a pivotal cause of excessive cytokine production, leading to cytokine storm and severe pathology in infectious diseases such as SARS and the ongoing COVID-19 pneumonia disease, RH might suggest promising therapeutic potential in the management of cytokine storm in these diseases.
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http://dx.doi.org/10.1016/j.phymed.2020.153350DOI Listing
December 2020

[The inhibiting role of recombinant plasmid PGCsi-AQP1 on laryngeal carcinoma in vivo].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2015 Nov;29(21):1886-9, 1893

Objective: To construct a kind of recombinant plasmid PGCsi-AQP1 delivery with DOPC and explore the inhibit effect of laryngeal carcinoma by RNAi targeting AQP1 in vivo.

Method: Male BALB/c mice, 6 weeks of age transplanted with laryngeal carcinoma cell line Hep-2, four groups were divided randomly: Tail vein injection group (TVIG), Carcinoma around injection group (CAIG), negative control group (NCG) and blank control group (BCG). The recombinant plasmid PGCsi-AQP1 delivery with DOPC were inject into tail vein or surrounding tumor. HE pathological slides and tumor size were observed and inhibitory rate was figured up. The level of AQP1 protein expression and high microvessel density were detected by Immunohistochemical staining (IHC).

Result: We constructed BALB/c mice models of laryngeal carcinoma successfully (1) HE staining: cell putrescence, nuclear pyknosis and apoptotic bodies were more in the tumor tissues of experimental groups than two control groups. (2) The total volumes of tumor in experimental group were both smaller than in two control groups (P < 0.01). The inhibition rate of TVIG and CAIG were 52.4% and 53.5% respectively and there was no significant difference (P > 0.05). (3) IHC: the AQP1 positive cells and microvessel density in TVIG and CAIG were both less than in two control groups (P < 0.01).

Conclusion: Neutral lipsomes DOPC could help carriaging the recombinant plasmid PGCsi-AQP1 to tumor and then play an inhibit role in laryngeal carcinoma tissue by RNAi targeting AQP1 in vivo.
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November 2015

[Correlation between the expression of aquaporin 1 and the micro-angiogenesis in laryngeal carcinoma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009 Mar;23(5):219-21

Department of Otorhinolaryngology-Head and Neck Surgery, China-Japan Friendship Hospital, Jilin University, Changchun, 130031, China.

Objective: To confirm the expression and distribution of aquaporin 1 in laryngeal carcinoma, and analyze the correlation to micro angiogenesis in the development of laryngeal carcinoma.

Method: The expression and distribution of aquaporin 1 were examined by immunohistochemical technique in laryngeal carcinoma. New vessels were labelled using CD105 monoclonal antibody. Systematic analysis had been done on IMVD and data of clinical pathology.

Result: Positive AQP1 cells and IMVD in primary carcinoma were higher than that in normal laryngeal mucosa. The expression of AQP1 was gradually increased with the decrease of differentiation grade of laryngeal carcinoma. The expression of AQP1 in lymphatic metastasis groups was higher than that of controls.

Conclusion: The expression of AQP1 in tumor cells and IMVD of primary laryngeal carcinoma are higher than normal. Not only is increased expression of AQP1 positive relevant to IMVD, but to lymphatic metastasis and malignant cell grading from laryngeal carcinoma. The increased AQP1 expression in epithelial cells of carcinoma and vascular endothelial cells may play a considerable role in growing, infiltrating, metastasis of malignant tumor by promoting vascular permeability.
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March 2009

[Effect of inhibiting aquaporin-1 on proliferation and apoptosis of the Hep-2 cell].

Lin Chuang Er Bi Yan Hou Ke Za Zhi 2006 Nov;20(21):988-91

Department of Otolaryngology-Head and Neck Surgery Chinese-Japanese Union Hospital, Bethune Faculty of Medicine, Jilin University, Changchun 130031, China.

Objective: To explore the effect of inhibiting aquaporin-1 (AQP-1) on proliferation and apoptosis of the Hep-2 cell.

Method: The expression of AQP-1 in Hep-2 cell was identified through immunohistochemistry. After using acetazolamide, an antagonist of AQP-1, the assay of cell proliferation, apoptosis and the expression of AQP-1 were performed by microculture tetrazolium salt(MTT) and flow cytometry, TUNEL respectively.

Result: The expression of AQP-1 is mainly found on membrane of Hep-2 cell and the expression is significantly reduced when the concentration of acetazolamide is 5 x 10(-5) mol/L. Noteworthily, inhibiting AQP-1 by acetazolamide, the rate of cell growth and cell apoptosis significantly increases with the time prolong. It showed time-dependent phenomena. There is positive relationship obviously between cell apoptosis rate and inhibition rate of the AQP-1 protein expression.

Conclusion: The inhibiting AQP-1 with acetazolamide may significantly induce apoptosis of Hep-2 cell. It suggest that AQP-1 may be as new target of therapy of laryngeal cancer.
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November 2006

[Expression of inducible nitric oxide synthase mRNA in epithelial cell of nasal mucosa is upregulated through Toll-like receptor-4].

Lin Chuang Er Bi Yan Hou Ke Za Zhi 2004 May;18(5):268-9

Department of Otorhinolaryngology-Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130031, China.

Objective: To investigate the upregulation of inducible nitric oxide synthase (iNOS) in epithelial cell of nasal mucosa through Toll-like receptor-4 (TLR-4).

Method: Specimens from 30 patients of chronic sinusitis and 21 healthy adults were examined by in situ hybridization for TLR-4 and iNOS mRNA.

Result: All 30 samples of chronic sinusitis showed a stronger expression of TLR-4 and iNOS than in controls (P<0.01). iNOS upregulated in nasal epithelium correlated with TLR-4 (r=0.435, P<0.01).

Conclusion: It suggested that TLR-4 may play a role in enhancing local host defence and inflammation via upregulating the expression of iNOS mRNA and the subsequent increased production of NO.
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May 2004

[Study on molecular mechanism of anti-aging effect of rhidosin on olfactory bulb in senile rats].

Lin Chuang Er Bi Yan Hou Ke Za Zhi 2003 Feb;17(2):100-1, 104

Department of Otorhinolaryngology-Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun 130031.

Objective: To research the molecular mechanism of anti-aging effect of rhidosin on olfactory bulb in senile rats.

Method: Ten 3 month-old rats and twenty 26-month-old rats were randomed in rhidosin and saline groups. After decapitated the rats, the olfactory bulb were cut and immediately fixed with neutral formation, followed with paraffin-embedding, serial sectioning, immunohistochemical staining and light microscopic observation.

Result: The proteins of FGF, Bcl-2 and Bax were mainly expressed in mitral cells in the olfactory bulb of the rats. The positive expression rate of FGF and Bcl-2 in young rats group was significantly higher than that in old rats group(P < 0.01). The FGF and Bcl-2 were positive relationship(r = 0.8971; P < 0.01). The expression of Bax in young control group was slightly lower than that in old control group, but there was no significant difference (P > 0.05). The positive expression rate of FGF and Bcl-2 in rhidosin group was significantly higher than that in control group in old rate group(P < 0.01).

Conclusion: FGF is a factor of ascending the anti-apoptosis gene Bcl-2 in mitral cells; rhidosin can increase the expression of FGF and Bcl-2 proteins. We guess that the mechanism of rhidosin anti-aging effect on the olfactory system may be through the effect of increasing the expression of FGF to inhibit the apoptosis of mitral cells.
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February 2003

[Immunoregulatory effect of Bacillus Calmette Guerin aerosol to allergic airway diseases].

Zhonghua Er Bi Yan Hou Ke Za Zhi 2002 Aug;37(4):267-70

Department of Otorhinolaryngeal-Head Neck Surgery, Chinese-Japan Union Hospital of Jilin University, Changchun 130031, China.

Objective: To investigate whether bacillus calmette guerin (BCG) is effective used transairway and its preventive mechanisms to allergic airway diseases.

Methods: Animal experiment was finished. Adult rats were devided into four groups: control group, ovalbumin-sensitized group, BCG used transairway group, BCG used transairway + ovalbumin-sensitized group. Then these animals symptoms were studied and the pathology change were studied under microscope about nasal and bronchi mucosa and bronchoalveolar lavege fluid cells. IL-4 mRNA and IFN-gamma mRNA in lung tissue were detected through RT-PCR, the protein production of IL-4 and IFN-gamma about bronchoalveolar lavege fluid and serum were detected through ELISA.

Results: In ovalbumin-sensitized group, allergic animal model were made successfully. In only BCG used transairway group, the symptoms of animals were normal, few inflammation cells infiltrated into the mucosa of nasal and bronchi, the numbers of macrophage were greatly increased in smear of bronchoalveolar lavege fluid, IFN-gamma mRNA and protein production were greatly increased. In BCG used transairway + ovalbumin-sensitized group, the allergic symptoms and inflammation were greatly reduced, not only IFN-gamma mRNA and protein production were increased but also IL-4 mRNA and protein production were greatly decreased.

Conclusion: It is a good pathway that BCG used transairway. The immunoloregulation mechanisms of BCG to allergic airway diseases are to enhance Th1 response, in the meantime, to suppress Th2 response.
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August 2002

Expression and significance of the vascular permeability factor in nasal polyps.

Chin Med J (Engl) 2002 Aug;115(8):1251-2

Department of ENT, Second Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.

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August 2002
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