Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Alzheimers Dis ; 82(4): 1635-1649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219730

RESUMO

BACKGROUND: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer's disease (AD); however, the exact effect and mechanism remain unknown. OBJECTIVE: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. METHODS: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. RESULTS: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-ß42 (Aß42) and Aß40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3ß (GSK3ß) inactivation via upregulating GSK3ß (pSer9). CONCLUSION: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aß production and tau phosphorylation, which is related to GSK3ß inactivation.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/metabolismo , Cognição/efeitos dos fármacos , Camundongos Transgênicos , Proteínas de Transferência de Fosfolipídeos/metabolismo , Proteínas tau/metabolismo , Animais , Encéfalo/patologia , Córtex Cerebral/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Teste do Labirinto Aquático de Morris , Fármacos Neuroprotetores/farmacologia , Fosforilação , Placa Amiloide/patologia
2.
Psychogeriatrics ; 21(4): 659-667, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33851473

RESUMO

Phospholipid transfer protein (PLTP) is a complex glycosylated protein that mediates the transfer of phospholipids, unesterified cholesterol, diacylglycerides, specific apolipoproteins, and tocopherols between different classes of lipoproteins as well as between lipoproteins and cells. Many studies have associated PLTP with a variety of lipid metabolic diseases. However, recent studies have indicated that PLTP is highly expressed in the brain of vertebrate and may be related to many central nervous system diseases, such as Alzheimer's disease. Here, we review the data and report the role and mechanisms PLTP in Alzheimer's disease.


Assuntos
Doença de Alzheimer , Proteínas de Transferência de Fosfolipídeos , Encéfalo/metabolismo , Colesterol , Humanos , Lipoproteínas , Proteínas de Transferência de Fosfolipídeos/metabolismo
3.
Sheng Li Xue Bao ; 73(1): 69-81, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33665662

RESUMO

Phospholipids are important components of biomembrane and lipoproteins. Phospholipids can be oxidized by free radicals/nonradicals and enzymes to form oxidized phospholipids (OxPLs), which can lead to further generation of oxidation products with different biological activities. Clinical evidence shows that OxPLs are constantly generated and transformed during the pathogenesis of atherosclerosis and accumulated at the lesion sites. OxPLs are highly heterogeneous mixtures that can influence the progress of atherosclerosis through a variety of related receptors or signaling pathways. This review summarizes the process of phospholipid oxidation, the related products, the interaction of OxPLs with endothelial cells, monocytes/macrophages, smooth muscle cells, platelets and lipoproteins involved in the pathological process of atherosclerosis, and the progress of the researches using OxPLs as a target to inhibit atherosclerosis in recent years.


Assuntos
Aterosclerose , Fosfolipídeos , Células Endoteliais , Humanos , Miócitos de Músculo Liso , Oxirredução
4.
Neurosci Bull ; 37(3): 389-404, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33078374

RESUMO

Molecular hydrogen (H2) is a physiologically inert gas. However, during the last 10 years, increasing evidence has revealed its biological functions under pathological conditions. More specifically, H2 has protective effects against a variety of diseases, particularly nervous system disorders, which include ischemia/reperfusion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, neurodegenerative diseases, cognitive dysfunction induced by surgery and anesthesia, anxiety, and depression. In addition, H2 plays protective roles mainly through anti-oxidation, anti-inflammation, anti-apoptosis, the regulation of autophagy, and preservation of mitochondrial function and the blood-brain barrier. Further, H2 is easy to use and has neuroprotective effects with no major side-effects, indicating that H2 administration is a potential therapeutic strategy in clinical settings. Here we summarize the H2 donors and their pharmacokinetics. Meanwhile, we review the effectiveness and safety of H2 in the treatment of various nervous system diseases based on preclinical and clinical studies, leading to the conclusion that H2 can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury, Parkinson's disease, and diseases characterized by cognitive dysfunction. The potential mechanisms involved in the neuroprotective effect of H2 are also analyzed.


Assuntos
Fármacos Neuroprotetores , Traumatismo por Reperfusão , Autofagia , Humanos , Hidrogênio , Mitocôndrias , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle
5.
Med Gas Res ; 9(3): 115-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552873

RESUMO

Advanced cancer treatment is a huge challenge and new ideas and strategies are required. Hydrogen exerts antioxidant and anti-inflammatory effects that may be exploited to control cancer, the occurrence and progression of which is closely related to peroxidation and inflammation. We conducted a prospective follow-up study of 82 patients with stage III and IV cancer treated with hydrogen inhalation using the "real world evidence" method. After 3-46 months of follow-up, 12 patients died in stage IV. After 4 weeks of hydrogen inhalation, patients reported significant improvements in fatigue, insomnia, anorexia and pain. Furthermore, 41.5% of patients had improved physical status, with the best effect achieved in lung cancer patients and the poorest in patients with pancreatic and gynecologic cancers. Of the 58 cases with one or more abnormal tumor markers elevated, the markers were decreased at 13-45 days (median 23 days) after hydrogen inhalation in 36.2%. The greatest marker decrease was in achieved lung cancer and the lowest in pancreatic and hepatic malignancies. Of the 80 cases with tumors visible in imaging, the total disease control rate was 57.5%, with complete and partial remission appearing at 21-80 days (median 55 days) after hydrogen inhalation. The disease control rate was significantly higher in stage III patients than in stage IV patients (83.0% and 47.7%, respectively), with the lowest disease control rate in pancreatic cancer patients. No hematological toxicity was observed although minor adverse reactions that resolved spontaneously were seen in individual cases. In patients with advanced cancer, inhaled hydrogen can improve patients' quality-of-life and control cancer progression. Hydrogen inhalation is a simple, low-cost treatment with few adverse reactions that warrants further investigation as a strategy for clinical rehabilitation of patients with advanced cancer. The study protocol received ethical approval from the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval number: Fuda20181207).


Assuntos
Hidrogênio/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relatório de Pesquisa , Inquéritos e Questionários , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Humanos , Hidrogênio/administração & dosagem , Hidrogênio/efeitos adversos , Hidrogênio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Estudos Retrospectivos , Segurança , Resultado do Tratamento , Adulto Jovem
6.
Life Sci ; 233: 116700, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356907

RESUMO

AIMS: Hydrogen (H2) has antioxidant effects. The pharmacologic function of H2 in platelets is not yet clear. Therefore, in this study we sought to investigate the inhibitory effects of H2 on in vitro platelet activation and in vivo prevention of thrombus formation. MAIN METHODS: After platelets were incubated with H2-rich saline (HRS), platelet adhesion in whole human blood was assessed in fibrinogen-coated perfusion chambers, while rat platelet aggregation induced by ADP, collagen and H2O2 was detected through light transmission aggregometry. The level of P-selectin, thromboxane B2, nitric oxide (NO), malondialdehyde, reactive oxygen species (ROS), cGMP, extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and fibrinogen binding to platelets were evaluated in vitro. Besides, the in vivo effects were examined in arterio-venous shunt thrombosis, FeCl3-induced artery thrombus formation, and tail bleeding time in mice and rats. KEY FINDINGS: HRS prolonged tail bleeding time in mice and rats, decreased thrombus weight and prolonged the time to occlusion in rat and mouse thrombosis models in vivo and inhibited platelet adhesion as well as aggregation in vitro. Additionally, HRS decreased P-selectin expression, release of thromboxane B2, ROS, and fibrinogen binding, but enhanced NO levels in H2O2-exposed platelets. HRS also decreased malondialdehyde levels in plasma of the rat arterial thrombosis or H2O2-exposed platelet model. Moreover, HRS increased cGMP level, decreased p-ERK1/2 (diminished with KT5823) in the platelets stimulated by H2O2. SIGNIFICANCE: These results suggest that H2 has antithrombotic effects, which may be due to its antioxidant property and subsequent inhibition of platelet activation via NO/cGMP/PKG/ERK pathway.


Assuntos
Antioxidantes/farmacologia , Hidrogênio/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Trombose/prevenção & controle , Animais , Biomarcadores/análise , Fibrinogênio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Adesividade Plaquetária , Ratos , Ratos Sprague-Dawley , Trombose/etiologia , Trombose/patologia
7.
Sheng Li Xue Bao ; 71(2): 371-377, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31008498

RESUMO

Molecular hydrogen (H2) has been shown to have diverse biomedical effects. As a small molecular gas, hydrogen can be diffused to the target without hindrance. A variety of related hydrogen products used in medical research and public health have been developed. There are various methods of administration of H2, mainly including inhaling hydrogen gas, drinking hydrogen water, injecting hydrogen-saline, orally taking solid-state H2 sustained-release agents, and stimulating intestinal microbiomes to produce hydrogen. Pharmacokinetics of H2 in vivo vary with methods of administration and thus influence its biomedical effects. This review summarizes the types of H2 donors and their pharmacokinetics in vivo.


Assuntos
Hidrogênio/administração & dosagem , Hidrogênio/farmacocinética
8.
Sheng Li Xue Bao ; 70(5): 557-564, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30377695

RESUMO

For a long time, hydrogen (H2) has been considered as a physiological inert gas. However, recent studies have demonstrated that molecular H2 exerts significant therapeutic effects on various disease models due to its antioxidative, anti-inflammatory and anti-apoptotic capabilities, which have also been well confirmed in many clinical trials. Cardiovascular and cerebrovascular diseases (CCVDs) are the leading cause of death in the world, constituting a serious threat to human life and public health. In this paper, we reviewed the latest research progress of the biomedical effects of H2 in CCVDs and its possible molecular mechanisms, in the hope of providing new clues for the treatment of some CCVDs.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Hidrogênio/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/prevenção & controle , Humanos
9.
Thromb Haemost ; 118(12): 2086-2097, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30419596

RESUMO

It remains unclear whether plasma phospholipid transfer protein (PLTP) is involved in hyper-coagulation or hypo-coagulation. This study investigated the direct effect of PLTP on platelet aggregation and the underlying mechanism. Washed platelets from humans or mice and mouse platelet-rich plasma and human recombinant PLTP were isolated. PLTP is present in human platelets. We assessed adenosine diphosphate (ADP)-, collagen- and thrombin-induced platelet aggregation, phosphatidylserine externalization and photothrombosis-induced cerebral infarction in mice. PLTP over-expression increased platelet aggregation, while PLTP deficiency had the opposing reaction. Human recombinant PLTP increased both mouse and human platelet aggregation in a dose-dependent manner. Phosphatidylserine externalization provides a water/lipid surface for the interaction of coagulation factors, which accelerates thrombosis. Compared with wild-type controls, platelets from PLTP transgenic mice had significantly more phosphatidylserine on the exterior surface of the plasma membrane, whereas platelets from PLTP-deficient mice had significantly less phosphatidylserine on the surface, thus PLTP influences fibrinogen binding on the plasma membrane. Moreover, recombinant PLTP together with ADP significantly increased phosphatidylserine exposure on the plasma membrane of PLTP-deficient platelets, thereby increasing fibrinogen binding. PLTP over-expression significantly accelerated the incidence of photothrombosis-induced infarction in mice, whereas PLTP deficiency significantly reduced the frequency of infarction. We concluded that PLTP promotes phosphatidylserine externalization at the plasma membrane of platelets and accelerates ADP- or collagen-induced platelet aggregation. This effect plays an important role in the initiation of thrombin generation and platelet aggregation under sheer stress conditions. Thus, PLTP is involved in hyper-coagulation. Therefore, PLTP inhibition could be a novel approach for countering thrombosis.


Assuntos
Plaquetas/fisiologia , Membrana Celular/metabolismo , Infarto Cerebral/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo , Trombofilia/metabolismo , Difosfato de Adenosina/metabolismo , Animais , Plaquetas/ultraestrutura , Membrana Celular/ultraestrutura , Células Cultivadas , Infarto Cerebral/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Fosfatidilserinas/metabolismo , Proteínas de Transferência de Fosfolipídeos/genética , Agregação Plaquetária/genética , Trombina/metabolismo , Trombofilia/genética
10.
Shanghai Kou Qiang Yi Xue ; 27(3): 252-256, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30411118

RESUMO

PURPOSE: To investigate the effect of hydrogen rich water on experimental gingivitis in SD rats during pregnancy. METHODS: Female SD rats mated with male ones were chosen to induce experimental gingivitis after ligation for 2 weeks. The pregnant rats were randomly divided into control group, model group and HW group. In the control and model group, rats were given pure water, while animals in the HW group were given hydrogen-rich water twice a day. All pregnant animals were sacrificed on day 16 of pregnancy. The level of Prog, SOD and TNF-α in the gingiva of different groups were measured by ELISA, the expression of PR, NFκB and TNF-α were determined by immunohistochemistry and Western blot. SPSS 13.0 software package was used for data analysis. RESULTS: Pregnancy gingivitis of SD rats could be induced by thread ligation. PR was mainly distributed in the gingival epithelium, while there was no significant difference of Prog and PR in the gingiva among different groups(P>0.05). Furthermore, in the model group, lower SOD level as well as higher NFκB and TNF-α level were found in the gingiva. Compared with the model group, the inflammatory response of pregnancy gingivitis in HW group was significantly suppressed along with decreased NFκB and TNF-α. CONCLUSIONS: Progesterone and its receptor may play an indirect role in the process of pregnancy gingivitis of rats. Hydrogen rich water may be beneficial in suppressing pregnancy gingivitis progress by decreasing inflammatory response related to gingival oxidative stress.


Assuntos
Gengivite , Hidrogênio , Complicações na Gravidez , Água , Animais , Feminino , Gengiva , Gengivite/terapia , Masculino , Gravidez , Complicações na Gravidez/terapia , Ratos , Ratos Sprague-Dawley
11.
Med Gas Res ; 8(3): 79-84, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319761

RESUMO

Dehydration is one of the intrauterine abnormalities that could lead to fetal growth retardation and to increase the risk of a variety of adult diseases later in life. This study were to determine the impact of hydrogen-rich water (HRW) supplementation on placental angiotensin II type 1 receptor and placental oxidative stress induced by water restriction. Pregnant Wistar rat were randomly assigned to one of the three groups (n =12 per group). In control group, pure water and food were supplied ad libitum. Water restriction group and HRW group were respectively given pure water and HRW with free access to food, excepting only one hour was available for drinking from day 7 to day 17 of pregnancy. The placental damages and biomarkers of stress were detected by histopathology, immunohistochemistry and western blot, as well as serological test were performed. We demonstrated that maternal water restriction resulted in reduced urine volume and increased serum osmotic pressure, along with decreased fetus weight and crown-rump length. Although placental weight and the number of fetuses had no significant difference among groups, the placental efficiency significantly increased after the oral administration of HRW to the mothers. Meanwhile, the serological derivatives of reactive oxygen metabolites decreased, a significant improvement of placental microstructure with more developed junctional zone and denser labyrinth was manifested, the upregulated expression of angiotensin II type 1 receptor, nuclear factoκB, malondialdehyde, 8-hydroxydeoxyguanosine, p38, c-Jun N-terminal kinase and down-regulation of superoxide dismutase were revealed in the placenta. Collectively, HRW administration is able to effectively attenuate placental stress induced by water restriction.

12.
Sheng Li Xue Bao ; 69(6): 767-774, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29270592

RESUMO

The purpose of this study was to investigate whether activating transcription factor 6 (ATF6), a sensor to endoplasmic reticulum stress (ERS), would mediate advanced glycated albumin (AGE-alb)-induced macrophage apoptosis and to elucidate the possible molecular mechanisms. RAW264.7 macrophages were cultured in vitro and treated with AGE-alb (2, 4 and 6 g/L), normal control albumin or tunicamycin (TM, 4 mg/L) for 24 h. ATF6 small interfering RNA (siRNA) was transfected to RAW264.7 cells by Lipofectamine 2000. Cell viability and apoptosis were determined by MTT method and Annexin V-FITC/propidium iodide apoptosis detection kit, respectively. The activities of lactate dehydrogenase (LDH) in medium and caspase-3 in cells were measured by corresponding detection kits. ATF6 nuclear translocation was detected by Western blot and immunofluorescence cytochemistry. Protein and mRNA levels of C/EBP homologous protein (CHOP, a key-signaling component of ERS-induced apoptosis) were detected by Western blot and real-time fluorescence quantitative PCR, respectively. The results showed that similar to TM, AGE-alb increased the expression of CHOP at both the protein and mRNA levels in a concentration dependent manner. ATF6, as a factor that positively regulates CHOP expression, was activated by AGE-alb in a concentration dependent manner. siRNA-mediated knockdown of ATF6 significantly inhibited AGE-alb-induced macrophage injury, as indicated by the increased cell viability and the decreased LDH release, apoptosis and caspase-3 activation. Additionally, ATF6 siRNA attenuated AGE-alb-induced CHOP upregulation at both the protein and mRNA levels. These results suggest that ATF6 and its downstream molecule CHOP are involved in AGE-alb-induced macrophage apoptosis.


Assuntos
Fator 6 Ativador da Transcrição/fisiologia , Apoptose/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Albumina Sérica/farmacologia , Fator de Transcrição CHOP/fisiologia , Animais , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Transdução de Sinais/fisiologia
13.
Sci Rep ; 7(1): 7333, 2017 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-28779128

RESUMO

This study was designed to explore the protective effect of D4F, an apolipoprotein A-I mimetic peptide, on nuclear factor-κB (NF-κB)-dependent Fas/Fas ligand (FasL) pathway-mediated apoptosis in macrophages induced by oxidized low-density lipoprotein (ox-LDL). Our results showed that ox-LDL induced apoptosis, NF-κB P65 nuclear translocation and the upregulation of Fas/FasL pathway-related proteins, including Fas, FasL, Fas-associated death domain proteins (FADD), caspase-8 and caspase-3 in RAW264.7 macrophages, whereas silencing of Fas blocked ox-LDL-induced macrophage apoptosis. Furthermore, silencing of P65 attenuated macrophage apoptosis and the upregulation of Fas caused by ox-LDL, whereas P65 expression was not significantly affected by treatment with Fas siRNA. D4F attenuated the reduction of cell viability and the increase in lactate dehydrogenase leakage and apoptosis. Additionally, D4F inhibited ox-LDL-induced P65 nuclear translocation and upregulation of Fas/FasL pathway-related proteins in RAW264.7 cells and in atherosclerotic lesions of apoE-/- mice. However, Jo2, a Fas-activating monoclonal antibody, reversed the inhibitory effect of D4F on ox-LDL-induced cell apoptosis and upregulation of Fas, FasL and FADD. These data indicate that NF-κB mediates Fas/FasL pathway activation and apoptosis in macrophages induced by ox-LDL and that D4F protects macrophages from ox-LDL-induced apoptosis by suppressing the activation of NF-κB and the Fas/FasL pathway.


Assuntos
Apolipoproteína A-I/farmacologia , Apoptose/efeitos dos fármacos , Proteína Ligante Fas/metabolismo , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor fas/metabolismo , Animais , Apolipoproteínas E/deficiência , Dieta Hiperlipídica , Células Espumosas/patologia , Lipoproteínas LDL/farmacologia , Camundongos , Transporte Proteico , Células RAW 264.7
14.
Sheng Li Xue Bao ; 69(4): 515-521, 2017 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-28825111

RESUMO

Autophagy is a cellular catabolic process responsible for removing the injured proteins and organelles via lysosome-dependent pathway, and it plays an important role in maintaining cellular homeostasis. Recent studies have shown that autophagy is activated and implicated in the pathogenesis of atherosclerosis. Autophagy can be triggered by oxidative lipids, cytokines and advanced glycation end products, and exerts protective or detrimental functions in the progression of atherosclerosis. However, the precise role and mechanisms of autophagy in different stages of atherosclerosis are still not fully clarified. This review highlights recent findings regarding autophagy response in vascular cells and its potential contribution to atherogenesis. Additionally, the relationship of autophagy with endoplasmic reticulum stress and whether autophagy could be a new therapeutic target for atherosclerosis are also discussed.


Assuntos
Aterosclerose/fisiopatologia , Autofagia , Estresse do Retículo Endoplasmático , Animais , Humanos , Lisossomos
15.
Sheng Li Xue Bao ; 69(2): 225-234, 2017 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-28435982

RESUMO

High-density lipoprotein (HDL) is composed of apolipoproteins, lipids and functional proteins. HDL protects against atherosclerosis (AS) by reverse cholesterol transport (RCT). HDL inhibits the lipid oxidation, inflammation and restores endothelial function. During systemic inflammation or metabolic disorders, HDL can be modified abnormally and converted to a dysfunctional type, which results in the loss of anti-inflammatory factors including apolipoprotein A-I (apoA-I), paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH), and gains of pro-inflammatory factors such as serum amyloid A (SAA), triglyceride (TG) and oxidative lipid. Therefore, understanding the changes in compositions and biological functions of dysfunctional HDL might help to comprehend its pathogenic mechanism.


Assuntos
Inflamação/sangue , Lipoproteínas HDL/fisiologia , Doenças Metabólicas/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Apolipoproteína A-I/sangue , Arildialquilfosfatase , Aterosclerose , Endotélio Vascular/fisiologia , Humanos , Metabolismo dos Lipídeos , Lipoproteínas HDL/sangue , Oxirredução , Proteína Amiloide A Sérica/metabolismo , Triglicerídeos/sangue
17.
BMC Complement Altern Med ; 15: 230, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26169264

RESUMO

BACKGROUND: Ethanol extract of propolis (EEP), rich in flavones, has been known for various biological activities including antioxidant, antiinflammatory and antibiotic activities. Our previous studies have shown that EEP protects endothelial cells from oxidized low-density lipoprotein (ox-LDL)-induced apoptosis and inhibits atherosclerotic lesion development. In this present study, we explored the protective effect of EEP on ox-LDL-induced cytotoxicity in macrophages and specifically the endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) pathway-mediated apoptosis. METHODS: EEP was prepared and the total flavonoids content of EEP was determined by the colorimetric method of Chinese Standard (GB/T 20574-2006). The effects of EEP on lipid accumulation, cytotoxicity and apoptosis in RAW264.7 cells induced by ox-LDL or tunicamycin (TM, an ER stress inducer) were assayed using oil red O staining, MTT assay, flow cytometric analysis and so on. Immunofluorescence, Western blot and real time-PCR analysis were then used to further investigate the molecular mechanisms by which EEP protects macrophages from ox-LDL-induced apoptosis. 4-phenylbutyric acid (PBA), an ER stress inhibitor, was used as a positive control. RESULTS: EEP (7.5, 15 and 30 mg/L) not only attenuated ox-LDL-induced lipid accumulation in RAW264.7 macrophages in a dose-dependent manner but also inhibited the decreased cell viability and the increased lactate dehydrogenase (LDH) leakage, caspase-3 activation and apoptosis induced by ox-LDL or tunicamycin (TM, a classical ER stress inducer), which were similar to 4-phenylbutyric acid (PBA, an inhibitor of ER stress) treatment. In addition, like PBA, EEP significantly suppressed the ox-LDL- or TM-induced activation of ER stress signaling pathway including the phosphorylation of double-stranded RNA-activated protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) as well as upregulation of glucose regulated protein 78 (GRP78) and the pro-apoptotic protein CHOP. Furthermore, EEP significantly suppressed ox-LDL intake by macrophages and the upregulation of CD36 induced by ox-LDL. CONCLUSION: These data indicate that EEP may protect macrophages from ox-LDL-induced apoptosis and the mechanism at least partially involves its ability to suppress the CD36-mediated ox-LDL intake and subsequent activation of ER stress-CHOP signalling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Antígenos CD36/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Macrófagos , Própole/farmacologia , Fator de Transcrição CHOP/metabolismo , Animais , Linhagem Celular , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos
18.
Heart Lung Circ ; 24(6): 602-10, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25533677

RESUMO

BACKGROUND: Infusion with hydrogen gas-saturated saline has recently been reported to exert antioxidant and anti-inflammatory activity that may protect against organ damage induced by oxidative stress. Therefore because oxidative stress plays a significant role in the pathophysiology of myocardial infarction (MI), the aim of our study was to investigate whether hydrogen-rich saline has cardioprotective effects against isoproterenol-induced MI in rats. METHODS: An acute MI model was induced in male Wistar rats by subcutaneous injection of isoproterenol. Different doses of hydrogen-rich saline (5, 7.5, and 10 mL/kg body weight i.p.) or Vitamin C (250 mg/kg body weight i.g.) were administered to the rats. Oxidative stress indices including levels of myocardial marker enzymes, inflammatory cytokines, membrane-bound myocardial enzymes and histopathological changes were measured. RESULTS: Compared with those in isoproterenol-MI group, hydrogen-rich saline decreased malondialdehyde and 8-hydroxy-desoxyguanosine concentrations, enhanced superoxide dismutase and Na(+)-K(+)-ATPase activity, lowered Ca(2+)-ATPase activity and decreased interleukin-6 and tumour necrosis factor-α levels in the serum and/or cardiac tissue of rats. Hydrogen-rich saline pretreatment also diminished infarct size, improved left heart function, and ameliorated pathological changes of the left heart. CONCLUSION: From these results, hydrogen-rich saline exerts cardiovascular protective effects against isoproterenol-induced MI at least in part via interactions which evoke antioxidant and anti-inflammatory activities.


Assuntos
Cardiotônicos/farmacologia , Hidrogênio/farmacologia , Isoproterenol/farmacologia , Infarto do Miocárdio/patologia , Cloreto de Sódio/farmacologia , Análise de Variância , Animais , Biomarcadores/sangue , Biópsia por Agulha , Citocinas/sangue , Modelos Animais de Doenças , Combinação de Medicamentos , Imuno-Histoquímica , Interleucina-6/sangue , Masculino , Infarto do Miocárdio/induzido quimicamente , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Wistar , Valores de Referência , Fator de Necrose Tumoral alfa/sangue
19.
Sheng Li Xue Bao ; 66(5): 612-8, 2014 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-25332008

RESUMO

The present study was to investigate whether endoplasmic reticulum stress (ERS) was involved in oxidized low density lipoprotein (ox-LDL)-induced scavenger receptor A1 (SR-A1) upregulation in macrophages. RAW264.7 cells were pretreated with 20 mmol/L of 4-phenylbutyric acid (PBA) for 30 min and then treated with ox-LDL (50 mg/L) for 12 h or stimulated with 2 mg/L tunicamycin (TM) or 2 µmol/L thapsigagin (TG) for 4 h. In addition, RAW264.7 cells were incubated with 0.5, 1 and 2 mg/L TM for 4 h or treated with 2 mg/L TM for 1, 2 and 4 h, respectively. The intracellular total cholesterol (TC) content was measured using a tissue/cell total cholesterol assay kit. The protein and mRNA expressions of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot and real-time PCR, respectively. Dil-ox-LDL uptake was detected using a microplate reader. The results showed that ox-LDL-induced cholesterol accumulation in macrophages was attenuated by PBA, an ERS inhibitor. Ox-LDL caused significant SR-A1 upregulation with concomitant activation of ERS as assessed by upregulation of GRP78, whereas PBA significantly inhibited the ox-LDL-induced SR-A1 upregulation (P < 0.05) and slightly decreased GRP78 expression by 39.3% (P = 0.057). TM, an ERS inducer, upregulated SR-A1 protein expression and ox-LDL uptake in dose- and time-dependent manner, but had no significant effect on SR-A1 mRNA level. However, the TM- or TG-induced SR-A1 upregulation and ox-LDL uptake were significantly mitigated by PBA. These data indicate that ERS plays a critical role in ox-LDL-induced SR-A1 upregulation, which in turn enhances the foam cell formation by uptaking more ox-LDL.


Assuntos
Estresse do Retículo Endoplasmático , Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Receptores Depuradores Classe A/metabolismo , Animais , Linhagem Celular , Colesterol/metabolismo , Proteínas de Choque Térmico/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Regulação para Cima
20.
Sheng Li Xue Bao ; 66(4): 489-95, 2014 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-25131792

RESUMO

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-inflammatory, antioxidant and antithrombotic properties and plays a protective role against atherosclerosis (AS). The purpose of the present study is to explore the effects of oxidized low density lipoprotein (ox-LDL) on the expression of PEDF in cultured human umbilical vein endothelial cells (HUVECs). HUVECs were cultured and incubated with ox-LDL at different concentrations (6.25, 12.5, 25, 50, 100 and 150 mg/L) for 24 h. Apoptosis of endothelial cells were assayed by morphological staining and flow cytometry. The intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Cell viability was assayed by MTT assay. PEDF protein and mRNA expressions in HUVECs were analyzed by Western blot and quantitative real-time PCR, respectively. The results showed that ox-LDL significantly induced apoptosis, reduced cell viability, increased intracellular ROS levels and decreased the PEDF expression in HUVECs in a concentration-dependent manner. Ox-LDL at 50 mg/L obviously decreased the PEDF protein expression compared with control group (P < 0.05), whereas 25 mg/L ox-LDL already markedly reduced the PEDF mRNA expression (P < 0.05). In conclusion, the results suggest that ox-LDL down-regulates the PEDF expression through an increased ox-LDL-induced intracellular production of ROS.


Assuntos
Proteínas do Olho/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , Fatores de Crescimento Neural/metabolismo , Serpinas/metabolismo , Apoptose , Células Cultivadas , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Espécies Reativas de Oxigênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...