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1.
Wiad Lek ; 74(2): 184-189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813469

RESUMO

OBJECTIVE: The aim: To investigate the utility of testing for chlamydial heat shock protein 60 (CHSP60) antibodies in the diagnosis of tubal infertility. PATIENTS AND METHODS: Materials and methods: All the collected samples were assayed for IgM and IgG antibodies to chlamydia trachomatis and chlamydial heat shock protein 60 (CHSP60) by using immunofluorescence and enzyme-linked immunosorbent assay (ELISA) techniques, respectively. RESULTS: Results: There were no substantial differences between antibodies to C. trachomatis in females with tubal infertility (67%) and non-tubal infertility (48%). However, women with tubal infertility (45%) have more anti-CHSP60 antibodies than non-tubal infertility (9%). Antibody screening for C. trachomatis has only (63%) sensitivity and (54%) specificity for detecting tubal infertility. On the other hand, the CHSP60 antibody testing has (44%) sensitivity and 92% specificity for diagnosing tubal infertility. A positive microimmunofluorescence (MIF) titer was observed in 12 of 18 (67%) females with the tubal problem, 31 of 64 (48%) with non-tubal infertility (P=0.3, OR=2.2, 95% CI=0.71 to 8.01). The CHSP60 antibodies were found in 8 of 18 (45%) females with tubal problem & 6 of 64 (9%) women with non-tubal infertility, power factor alpha α P=0.004, OR=9.3, 95% CI=2.1 to 43.2, power= 1.002 for n= 0.05). Incorporating CHSP60 and C. trachomatis antibodies testing gives an excellent positive probability proportion of 10 to diagnose C. trachomatis associated tubal infertility. CONCLUSION: Conclusions: CHSP60 antibody testing is a more specific evaluation than antibody testing for C. trachomatis for predicting chlamydia-associated tubal infertility. Using these tests at the first infertility examination may help the immediate diagnosis for non-interceptive tubal infertility.


Assuntos
Infecções por Chlamydia , Infertilidade Feminina , Anticorpos Antibacterianos , Chaperonina 60 , Infecções por Chlamydia/complicações , Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis , Feminino , Proteínas de Choque Térmico , Humanos , Infertilidade Feminina/diagnóstico , Estudos Prospectivos
2.
Anticancer Res ; 41(3): 1271-1282, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788718

RESUMO

BACKGROUND/AIM: We aimed to investigate the synergistic effects of apigenin and curcumin on the cross-talk between apoptosis and autophagic cell death, as well as on paraptosis in HeLa cells. MATERIALS AND METHODS: Cell viability was measured using the MTT assay. Synergistic effects were measured using the Bliss independence model. qRT-PCR was used to study the expression of genes related to apoptosis, autophagic cell death, and cross-talk. GRP78/BiP immunostaining was used to identify endoplasmic reticulum (ER) stress. RESULTS: Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29- to 27.6-fold. The combination of curcumin and apigenin showed a synergistic anti-tumor effect via cross-talk between processes leading to apoptosis and autophagic cell death, as well as ER stress-associated paraptosis. GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells. CONCLUSION: The combination of curcumin and apigenin is an effective potential therapeutic for cervical cancers.


Assuntos
Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Morte Celular Autofágica/efeitos dos fármacos , Curcumina/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Caspase 3/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Células HeLa , Proteínas de Choque Térmico/análise , Humanos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias do Colo do Útero/tratamento farmacológico
3.
Animal ; 15(2): 100106, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33712219

RESUMO

High environmental temperatures are a foremost concern affecting poultry production; thus, understanding and controlling such conditions are vital to successful production and welfare of poultry. In view of this, a completely randomized design with a 2 × 2 factorial arrangement involving two local strains (Kirin chicken (KC) and Three-yellow chicken (TYC)) and two temperature groups (normal/control = 30 ±â€¯2 °C and acute heat stress (AHS) = 35 ±â€¯1 °C for 8-h with 70% humidity) was used to assess the main regulatory factors such as heat shock protein (HSP70) gene, cytokine genes (IL-1ß, IL-6, IL-10), muscle development gene (IGF-1) and tissue histopathological changes. At 56 days old, the temperatures of the comb (CT), feet (FT), eyelid (ET) and rectal (RT) from each group were taken thrice at 0, 2, 4 and 8-h during AHS, and 1 and 3-h recovery period after AHS. At 80 days old, the slaughter weight was also analyzed. The CT and ET of the AHS groups increased during the 8-h trial, while the RT of both strains decreased significantly at 4 h but increased at 8 h in the TYC group. All temperature recordings dropped in the AHS groups of both strains during the recovery period. The results revealed that the mRNA expression of HSP70 in the liver was higher in the heat-stressed group of both strains compared to the control. The expression of HSP70 was shown in the AHS-KC group to be significantly high compared to the control (P < 0.05). Moreover, the IGF1 gene in the liver, breast muscle and leg muscle was downregulated in the AHS-TYC group compared to the control (P < 0.05), although that in the AHS-KC was downregulated in the breast muscle. The mRNA expression of spleen IL-1ß significantly decreased in the AHS-TYC group (P < 0.01), whereas that of the AHS-KC had no significant difference (P > 0.05). The mRNA expression of spleen IL-6 and IL-10 was increased in the AHS-KC group but did not exhibit obvious changes in the AHS-TYC. Correspondingly, the histopathological examinations revealed tissue injury in the AHS groups of both strains, with the TYC strain experiencing more severe changes. The final live and carcass weights showed a significant enhancement in the treatments (P < 0.01 and P < 0.05, respectively) and treatment×strain interaction (P < 0.05) with breast muscle rate significantly reducing among the treatments (P < 0.01) at 80 days. In conclusion, the differential response to AHS after physiological, molecular and immune response portrays KC to have better thermal tolerance than the TYC.


Assuntos
Galinhas , Transtornos de Estresse por Calor , Animais , Galinhas/genética , Proteínas de Choque Térmico HSP70/genética , Transtornos de Estresse por Calor/veterinária , Proteínas de Choque Térmico , Resposta ao Choque Térmico/genética , Temperatura Alta , Estresse Fisiológico
4.
Aquat Toxicol ; 233: 105771, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33578303

RESUMO

Present study aims to investigate interaction of molecular chaperons (heat shock protein 70, heat shock protein 90) with transcriptional factors (nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) to evaluate their role during metal induced stress in fish hepatocytes. Adult Puntius ticto were exposed to lead nitrate at 0 mg/l (control), 1/50th (0.04 mg/l) and 1/20th (0.12 mg/l) of LC50 for 30 days and sacrificed to collect liver tissues. Activity of selected liver enzymes, antioxidants and metallothionein were analyzed. Levels of heat shock protein 70, heat shock protein 90, nuclear factor kappa B, nuclear factor E2-related factor 2 and Kelch-like ECH-associated protein 1 were also measured. Liver enzymes showed a significant increase (p < 0.05) in both Pb exposed groups indicating that the liver might be at risk of damage. Increased level of lipid peroxidation due to metal stress was marked by significant increase (p < 0.05) in malondialdehyde level in fish exposed to the higher Pb concentration compared to control (+ 13.7 %). Significant increase (p < 0.05) in gluthathione reductase (+ 35 %, + 39.2 %), glutathione s-transferase (+ 22.4 %, + 50.4 %) activities and decrease in reduced glutathione level (- 6.75 %, - 12.25 %) in fish exposed to both lower and higher Pb concentration compared to control also indicated metal induced oxidative damage in fish liver. Super oxide dismutase and catalase activities increased significantly (p < 0.05) during exposure to lower Pb concentration, while decreased significantly (p < 0.05) during exposure to higher Pb concentration compared to those in control. Significant (P < 0.05) increase (+ 52.63 %, + 89.47 %) in metallothionein in Pb exposed groups confirmed its role in detoxification process of the metal. Heat shock protein 70 and heat shock protein 90 expression levels increased significantly (p < 0.05) during metal exposure indicating their role as modulator of stress-induced antioxidant protein remodelling. A positive correlation between nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1 with gluthathione regulatory enzymes (gluthathione reductase and glutathione s-transferase) was noted. Current study effectively illuminates the critical role of different factors (heat shock proteins/nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) to influence the expression and synthesis of antioxidants and other functional enzymes in lead-exposed fish liver.


Assuntos
Antioxidantes/metabolismo , Cyprinidae/metabolismo , Proteínas de Choque Térmico/metabolismo , Chumbo/toxicidade , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Nitratos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
5.
Medicine (Baltimore) ; 100(3): e24274, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546049

RESUMO

BACKGROUND: Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies. Several studies have reported paradoxical evidence of the association between HSP expression and prognosis of oral cancer. To address the discrepancy, we carried out the meta-analysis to assess the role of HSP such as: HSP70, HSP90, HSP27, HSP60, and HSP105 in susceptibility, progression, and prognosis of oral cancer. MATERIALS AND METHODS: We retrieved the PubMed, Embase, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to acquire the eligible studies which were associated with HSP70, HSP90, HSP27, HSP60, and HSP105 protein expression and oral cancer. We applied hazard ratio (HR) and its 95% confidence interval (95% CI) to assess the value of HSP protein expression in overall survival of oral cancer; odds ratio (OR) and its 95% CI were used to evaluate the association of risk and clinical features of oral cancer. Funnel plot, Begg test, and Egger line regression test were utilized to observe publication bias among studies. All statistical analysis was performed with Stata 14.0 software (Stata Corporation, College Station, TX). RESULTS: A total of 26 studies were included in the present meta-analysis. On based of the results, HSP70 and HSP27 had no significant association with progression of oral cancer. However, the pooled HR and 95% CI revealed a significant well effects of HSP70 and HSP27 expression on survival of oral cancer. Moreover, the susceptibility of oral cancer was significantly associated with HSP70 and HSP60 overexpression. CONCLUSION: HSP70 and HSP27 protein overexpression might be valuable biomarkers for the prognosis of oral cancer. And HSP70 and HSP60 might have potential predictive effects on the risk of oral cancer.


Assuntos
Proteínas de Choque Térmico/análise , Neoplasias Bucais/sangue , Prognóstico , Proteínas de Choque Térmico HSP70/análise , Proteínas de Choque Térmico HSP70/sangue , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/sangue , Proteínas de Choque Térmico/metabolismo , Humanos , Neoplasias Bucais/fisiopatologia , Modelos de Riscos Proporcionais
6.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537813

RESUMO

The activation of oxidative stress is a primary cause of chondrocyte apoptosis in osteoarthritis (OA). The 78­kDa glucose­regulated protein (GRP78)/mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated to be linked with the endoplasmic reticulum (ER) and autophagy. Hydrogen sulfide (H2S) has been reported to exert antioxidant effects. The present study investigated oxidative stress levels via 2',7'­dichlorofluorescin diacetate and MitoSOX staining, apoptosis rates via flow cytometry and the expression levels of ER stress­related proteins in GYY4137 (donor of H2S)­treated chondrocytes (CHs). CHs were isolated from the bilateral hip joints of male rats to examine mitochondrial permeability transition pore opening­ and mTOR signaling pathway­related proteins. The results demonstrated that tert­Butyl hydroperoxide (TBHP) increased CH apoptosis, and treatment with GYY4137 ameliorated TBHP­mediated the generation of ROS and CH apoptosis. Moreover, TBHP­treated CHs displayed elevated ER stress sensor expression levels and apoptotic rates; however, the TBHP­induced protein expression levels were decreased following GYY4137 treatment. In the present study, treatment with either GYY4137 or transfection with GRP78 siRNA both suppressed the activation of p­P70S6k and p­mTOR. H2S played an important role in regulating ER stress in TBHP­stimulated CHs. GYY4137 promoted autophagy, which was accompanied by the inhibition of ER stress. On the whole, the present study demonstrates that TBHP­induced oxidative stress stimulates ER interactions and CH apoptosis, which are suppressed by exogenous H2S via modulating the GRP78/mTOR signaling pathway.


Assuntos
Condrócitos/metabolismo , Condrócitos/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Sulfeto de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/farmacologia , Condrócitos/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Masculino , Morfolinas/química , Morfolinas/farmacologia , Compostos Organotiofosforados/química , Compostos Organotiofosforados/farmacologia , Peróxidos/farmacologia , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Cell Stress Chaperones ; 26(2): 289-295, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33559835

RESUMO

Members of the Cell Stress Society International (CSSI), Patricija van Oosten-Hawle (University of Leeds, UK), Mehdi Mollapour (SUNY Upstate Medical University, USA), Andrew Truman (University of North Carolina at Charlotte, USA) organized a new virtual meeting format which took place on November 5-6, 2020. The goal of this congress was to provide an international platform for scientists to exchange data and ideas among the Cell Stress and Chaperones community during the Covid-19 pandemic. Here we will highlight the summary of the meeting and acknowledge those who were honored by the CSSI.


Assuntos
Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico/genética , Humanos , Chaperonas Moleculares/genética , Proteostase/genética , Proteostase/fisiologia
8.
Medicine (Baltimore) ; 100(5): e23464, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592824

RESUMO

ABSTRACT: Brain natriuretic peptide is an established, surrogate follow-up marker, strongly correlated with heart failure severity. Several other biomarkers and tests are useful for assessing the prognosis of patients with HF, such as oxidized low-density lipoprotein antibodies and C-reactive protein. Some inflammatory cells, including monocytes, lymphocytes, and neutrophils, are involved in coronary heart disease and may be useful for prognosis also. This study assessed the potential usefulness of various laboratory biomarkers in predicting long-term outcomes and hospitalization among a cohort of outpatients with chronic, advanced HF.This retrospective, 18-year follow-up study included all patients admitted to the Heart Failure Outpatient Unit in our tertiary care medical center from 2000 through 2001 due to chronic HF. Excluded were patients with malignant disease, severe stroke, active inflammatory disease, or infection. At the first visit, blood was sampled for routine analysis and biomarkers NT-proBNP, C-reactive protein, myeloperoxidase, heat shock protein, and antibodies to oxidized low density lipoprotein. left ventricular ejection fraction and New York Heart Association class class were also established. Patients were followed every 3 months. Study endpoints were mortality or first hospitalization.Among 305 study patients, HF duration ranged from 2 months to 18 years. Mean follow-up was 9.1 ±â€Š6 years. Mean time to first hospitalization was 60 ±â€Š58.1 months, median = 38 (range 0-179). Mortality rate was 41%. Regression analysis showed New York Heart Association class, lymphocyte count and alkaline phosphatase were independent predictors of survival, with hazard ratios of 1.0, 0.973, and 1.006, respectively (P < .05).N-terminal pro-B-type natriuretic peptide, alkaline phosphatase, and lymphocyte count are important prognostic predictors for very long-term follow-up among patients with chronic HF.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Pressão Sanguínea , Peso Corporal , Proteína C-Reativa/análise , Doença Crônica , Comorbidade , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Frequência Cardíaca , Proteínas de Choque Térmico/sangue , Testes Hematológicos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Peroxidase/sangue , Estudos Retrospectivos , Fatores Sexuais , Função Ventricular Esquerda
9.
Vet Res ; 52(1): 30, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618766

RESUMO

Host proteins interacting with pathogens are receiving more attention as potential therapeutic targets in molecular medicine. Streptococcus suis serotype 2 (SS2) is an important cause of meningitis in both humans and pigs worldwide. SS2 Enolase (Eno) has previously been identified as a virulence factor with a role in altering blood brain barrier (BBB) integrity, but the host cell membrane receptor of Eno and The mechanism(s) involved are unclear. This study identified that SS2 Eno binds to 40S ribosomal protein SA (RPSA) on the surface of porcine brain microvascular endothelial cells leading to activation of intracellular p38/ERK-eIF4E signalling, which promotes intracellular expression of HSPD1 (heat-shock protein family D member 1), and initiation of host-cell apoptosis, and increased BBB permeability facilitating bacterial invasion. This study reveals novel functions for the host-interactional molecules RPSA and HSPD1 in BBB integrity, and provides insight for new therapeutic strategies in meningitis.


Assuntos
Barreira Hematoencefálica , Células Endoteliais/metabolismo , Fosfopiruvato Hidratase/metabolismo , Proteínas Ribossômicas/metabolismo , Infecções Estreptocócicas/veterinária , Streptococcus suis/metabolismo , Animais , Apoptose , Técnicas de Cocultura , Células Endoteliais/microbiologia , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Camundongos , Ligação Proteica , Sorogrupo , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Streptococcus suis/patogenicidade , Suínos , Doenças dos Suínos/microbiologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Nat Struct Mol Biol ; 28(2): 162-172, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33398175

RESUMO

Many proteins are transported into the endoplasmic reticulum by the universally conserved Sec61 channel. Post-translational transport requires two additional proteins, Sec62 and Sec63, but their functions are poorly defined. In the present study, we determined cryo-electron microscopy (cryo-EM) structures of several variants of Sec61-Sec62-Sec63 complexes from Saccharomyces cerevisiae and Thermomyces lanuginosus and show that Sec62 and Sec63 induce opening of the Sec61 channel. Without Sec62, the translocation pore of Sec61 remains closed by the plug domain, rendering the channel inactive. We further show that the lateral gate of Sec61 must first be partially opened by interactions between Sec61 and Sec63 in cytosolic and luminal domains, a simultaneous disruption of which completely closes the channel. The structures and molecular dynamics simulations suggest that Sec62 may also prevent lipids from invading the channel through the open lateral gate. Our study shows how Sec63 and Sec62 work together in a hierarchical manner to activate Sec61 for post-translational protein translocation.


Assuntos
Eurotiales/metabolismo , Proteínas de Choque Térmico , Proteínas de Membrana Transportadoras , Modelos Moleculares , Canais de Translocação SEC , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Processamento de Proteína Pós-Traducional , Transporte Proteico , Canais de Translocação SEC/química , Canais de Translocação SEC/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
11.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466228

RESUMO

Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia worldwide and is associated with ischemic stroke, heart failure, and substantial morbidity and mortality. Unfortunately, current AF therapy is only moderately effective and does not prevent AF progression from recurrent intermittent episodes (paroxysmal) to persistent and finally permanent AF. It has been recognized that AF persistence is related to the presence of electropathology. Electropathology is defined as structural damage, including degradation of sarcomere structures, in the atrial tissue which, in turn, impairs electrical conduction and subsequently the contractile function of atrial cardiomyocytes. Recent research findings indicate that derailed proteostasis underlies structural damage and, consequently, electrical conduction impairment. A healthy proteostasis is of vital importance for proper function of cells, including cardiomyocytes. Cells respond to a loss of proteostatic control by inducing a heat shock response (HSR), which results in heat shock protein (HSP) expression. Emerging clinical evidence indicates that AF-induced proteostasis derailment is rooted in exhaustion of HSPs. Cardiomyocytes lose defense against structural damage-inducing pathways, which drives progression of AF and induction of HSP expression. In particular, small HSPB1 conserves sarcomere structures by preventing their degradation by proteases, and overexpression of HSPB1 accelerates recovery from structural damage in experimental AF model systems. In this review, we provide an overview of the mechanisms of action of HSPs in preventing AF and discuss the therapeutic potential of HSP-inducing compounds in clinical AF, as well as the potential of HSPs as biomarkers to discriminate between the various stages of AF and recurrence of AF after treatment.


Assuntos
Fibrilação Atrial/metabolismo , Proteínas de Choque Térmico/metabolismo , Animais , Átrios do Coração/metabolismo , Resposta ao Choque Térmico/fisiologia , Humanos , Contração Miocárdica/fisiologia , Miócitos Cardíacos/metabolismo , Proteostase/fisiologia
12.
Gene ; 778: 145460, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33515727

RESUMO

BACKGROUND: Traditional Chinese medicine manipulation (TCMM) is often used to treat human skeletal muscle injury, but its mechanism remains unclear due to difficulty standardizing and quantifying manipulation parameters. METHODS: Here, dexamethasone sodium phosphate (DSP) was utilized to induce human skeletal muscle cell (HSkMC) impairments. Cells in a three-dimensional environment were divided into the control normal group (CNG), control injured group (CIG) and rolling manipulation group (RMG). The RMG was exposed to intermittent pressure imitating rolling manipulation (IPIRM) of TCMM via the FX­5000™ compression system. Skeletal muscle damage was assessed via the cell proliferation rate, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and creatine kinase (CK) activity. Isobaric tagging for relative and absolute protein quantification (iTRAQ) and bioinformatic analysis were used to evaluate differentially expressed proteins (DEPs). RESULTS: Higher-pressure IPIRM ameliorated the skeletal muscle cell injury induced by 1.2 mM DSP. Thirteen common DEPs after IPIRM were selected. Key biological processes, molecular functions, cellular components, and pathways were identified as mechanisms underlying the protective effect of TCMM against skeletal muscle damage. Some processes (response to oxidative stress, response to wounding, response to stress and lipid metabolism signalling pathways) were related to skeletal muscle cell injury. Western blotting for 4 DEPs confirmed the reliability of iTRAQ. CONCLUSIONS: Higher-pressure IPIRM downregulated the CD36, Hsp27 and FABP4 proteins in oxidative stress and lipid metabolism pathways, alleviating excessive oxidative stress and lipid metabolism disorder in injured HSkMCs. The techniques used in this study might provide novel insights into the mechanism of TCMM.


Assuntos
Antígenos CD36/metabolismo , Dexametasona/análogos & derivados , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Fibras Musculares Esqueléticas/citologia , Manipulações Musculoesqueléticas/métodos , Fenômenos Biomecânicos , Técnicas de Cultura de Células , Células Cultivadas , Dexametasona/efeitos adversos , Regulação para Baixo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Medicina Tradicional Chinesa , Modelos Biológicos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Transdução de Sinais
13.
Food Chem ; 348: 129134, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516993

RESUMO

In this study, similarities and differences of sodium tripolyphosphate (STPP) and sodium trimetaphosphate (STMP) pre-soaking on the stability of muscle proteins in shrimp were investigated during 12 weeks of frozen storage (-30 °C). The physicochemical analysis indicated significant improvements in the WHC, springiness, chewiness, and thermal stability of STPP and STMP pre-soaked samples when compared to the control. Interestingly, STMP pre-soaking showed better cryoprotective effects than the STPP treatment when the storage period reached the end of the 12 weeks. Furthermore, the label-free based proteomics results indicated that 62 upregulated differentially abundant proteins (DAPs) were detected in STMP when compared to STPP. These identified DAPs specifically included 40S ribosomal proteins, actin-related proteins, heat shock proteins, myosin heavy chain, and tubulin beta chain. Additionally, the gene ontology (GO) and eukaryotic clusters of orthologous group (KOG) analyses verified that the incorporation of STMP molecules enhanced the resistance of cytoskeleton proteins to cold-temperature stress.


Assuntos
Armazenamento de Alimentos/métodos , Penaeidae/metabolismo , Polifosfatos/química , Alimentos Marinhos/análise , Animais , Cromatografia Líquida de Alta Pressão , Congelamento , Proteínas de Choque Térmico/metabolismo , Penaeidae/química , Peptídeos/análise , Proteínas de Frutos do Mar/metabolismo , Espectrometria de Massas em Tandem , Fatores de Tempo
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(1): 75-78, 2021 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-33509756

RESUMO

OBJECTIVE: To explore the association between rare HSPB1 variants and amyotrophic lateral sclerosis (ALS). METHODS: We performed next-generation sequencing for 166 Chinese ALS patients to screen for possible pathogenic rare variants of HSPB1. The control individuals were obtained from 1000 Genome Project and an in-house whole-exome sequencing database. The Sequence Kernel Association Test (SKAT) and the SKAT-optimal test (SKAT-O) were used to identify the association between rare HSPB1 variants and ALS. RESULTS: We identified 3 possible pathogenic rare variants of HSPB1 (all were missenses), including c.379C>T (p.R127W), c.446A>C (p.D149A) and c.451A>C (p.T151P). Compared with 1000 Genome Project, SKAT p=3.61×10-7 and SKAT-O p=1.62×10-6; while compared with the in-house database, SKAT p=9.99×10-4, SKAT-O p= 1.80×10-3. We analyzed the phenotypes of rare HSPB1 variant carriers and found no specific clinical characteristics associated with these variants. CONCLUSIONS: Rare variants of HSPB1 are probably associated with the pathogenesis of ALS.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/genética , Grupo com Ancestrais do Continente Asiático , Proteínas de Choque Térmico , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Chaperonas Moleculares , Fenótipo
15.
Life Sci ; 269: 119094, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33482193

RESUMO

AIM: Environmental heat stress alters physiological and biochemical functions which leads to multiorgan dysfunction including severe hepatic injury in animals. We hypothesize that heat preconditioning can be potential intervention in combating heat illnesses. MAIN METHODS: Sprague Dawley rats were exposed to moderate heat stress, severe heat stress and heat preconditioning in heat simulation chamber. Mean arterial pressure, heart rate, skin and core temperature were monitored in pre and post heat exposed animals. After stress exposure, blood for hemodynamic and liver tissue for liver function tests, oxidative stress, inflammatory variables and structural studies were collected from rats. Hepatic mitochondria were isolated to study the key structural alterations and functional changes by transmission electron microscopy. KEY FINDINGS: The effect of heat precondition shows improvement in time to attain the core temperature, weight loss, blood pressure and heart rate in rats. Results exhibited decreased levels of liver function tests, elevated levels of free radicals and inflammatory cytokines in heat exposed liver as compared with heat preconditioned animals. Expression levels of mitochondrial heat shock protein 60, superoxide dismutase 1 and uncoupling protein 1 along with activity of electron transport chain complexes I-V were examined and found to be increased in heat preconditioned as compared to heat stressed animals. Morphological studies of liver parenchyma demonstrated reduction in structural deterioration of hepatic lobules and restoration of mitochondrial structural integrity in heat preconditioned rats. SIGNIFICANCE: Present study suggests that heat preconditioning intervention plays a crucial role in protection against heat induced hepatic injury in animals.


Assuntos
Metabolismo Energético , Transtornos de Estresse por Calor/terapia , Resposta ao Choque Térmico , Temperatura Alta , Fígado/metabolismo , Estresse Oxidativo , Animais , Transtornos de Estresse por Calor/etiologia , Transtornos de Estresse por Calor/metabolismo , Transtornos de Estresse por Calor/patologia , Proteínas de Choque Térmico/metabolismo , Fígado/lesões , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Oxirredução , Ratos , Ratos Sprague-Dawley
16.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498183

RESUMO

The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to mediate host cell entry. However, studies have reported viral susceptibility in intra- and extrapulmonary immune and non-immune cells lacking ACE2, suggesting that the S protein may exploit additional receptors for infection. Studies have demonstrated interactions between S protein and innate immune system, including C-lectin type receptors (CLR), toll-like receptors (TLR) and neuropilin-1 (NRP1), and the non-immune receptor glucose regulated protein 78 (GRP78). Recognition of carbohydrate moieties clustered on the surface of the S protein may drive receptor-dependent internalization, accentuate severe immunopathological inflammation, and allow for systemic spread of infection, independent of ACE2. Furthermore, targeting TLRs, CLRs, and other receptors (Ezrin and dipeptidyl peptidase-4) that do not directly engage SARS-CoV-2 S protein, but may contribute to augmented anti-viral immunity and viral clearance, may represent therapeutic targets against COVID-19.


Assuntos
/metabolismo , /fisiologia , Internalização do Vírus , /imunologia , Animais , Progressão da Doença , Proteínas de Choque Térmico/imunologia , Proteínas de Choque Térmico/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Neuropilina-1/imunologia , Neuropilina-1/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
18.
Phytomedicine ; 80: 153384, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33113507

RESUMO

BACKGROUND: Ling Zhi-8 (LZ-8) and GMI are two fungal immunomodulatory proteins (FIPs) with a similar structure and amino acid sequence and are respectively obtained from the medicinal mushroom Ganoderma lucidum and Ganoderma microsporum. They present the anti-cancer progression and metastasis. We previously demonstrated that LZ-8 reduces the tumor progression in lung cancer LLC1 cell-bearing mouse. However, it is unclear whether these FIPs induce changes in the protein expression profile in cancer cells and the mechanism for such a process is not defined. PURPOSE: This study determines the changes in the proteomic profile for tumor lesions of LLC1 cell-bearing mouse received with LZ-8 and the potential mechanism for FIPs in anti-lung cancer cells. METHODS: The proteomic profile of tumor lesions was determined using two-dimensional electrophoresis and a LTQ-OrbitrapXL mass spectrometer (LC-MS/MS). The biological processes and the signaling pathway enrichment analysis were performed using Ingenuity Pathway Analysis (IPA). The differentially expressed proteins were verified by Western blot. Cell viability was determined by MTT assay. Cell morphology was characterized using electron microscopy. Migration was detected using the Transwell assay. The apoptotic response was determined using Western blot and flow cytometry. RESULTS: Obtained results showed that 21 proteins in the tumor lesions exhibited differential (2-fold change, p < 0.05) expression between PBS and LZ-8 treatment groups. LZ-8-induced changes in the proteomic profile that may relate to protein degradation pathways. Specifically, three heat shock proteins (HSPs), HSP60, 70 and 90, were significantly downregulated in tumor lesions of LLC1-bearing mouse received with LZ-8. Both LZ-8 and GMI reduced the protein levels for these HSPs in lung cancer cells. Functional studies showed that they inhibited cell migration but effectively induced apoptotic response in LLC1 cells in vitro. In addition, the inhibitors of HSP60 and HSP70 effectively inhibited cell migration and decreased cell viability of LLC1 cells. CONCLUSIONS: LZ-8 induced changes in the proteomic profile of tumor lesions which may regulate the HSPs-related cell viability. Moreover, inhibition of HSPs may be related to the anti-lung cancer activity.


Assuntos
Proteínas Fúngicas/farmacologia , Ganoderma/química , Proteínas de Choque Térmico/metabolismo , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Regulação para Baixo/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteômica/métodos , Espectrometria de Massas em Tandem , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Ecotoxicol Environ Saf ; 209: 111671, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360290

RESUMO

Lead (Pb) is a toxic heavy metal pollutants and can damage male reproductive function. Selenium (Se) possesses an ability of antagonizing Pb toxicity. However, biological events in the process of Pb toxicity and mitigative effect of Se are not well understood. The aim of present research was to investigate potential mechanism of Se against Pb toxicity from the perspective of oxidative stress, heat shock response and autophagy in the spermatogonia and Leydig cell of chicken. The cells from one-day-old male Hyline chickens were treated with Se (0.5 µmol/L) and/or Pb (20 µmol/L) for 24 h, respectively. Cell viability, cell ultrastucture, Pb and Se concentrations, testosterone level, oxidative stress indicators and relative expression of heat shock proteins (HSPs) and autophagy-related genes were measured. The results showed that spermatogonia was more tolerant to Pb than Leydig cell; cell injury was confirmed via histological assessment, cell viability and testosterone level; oxidative stress was further indicated by the decrease of catalase, glutathione peroxidase, glutathione-s-transferase and superoxide dismutase activities and the increase of malondialdehyde and reactive oxygen species contents. Pb increased expression of HSPs (27, 40, 60, 70 and 90). Meanwhile Pb induced autophagy through up-regulation of autophagy-related proteins 5, Beclin 1, Dynein, light chain 3 (LC3)-I and LC3-II and down-regulation of mammalian target of rapamycin in two type cells of chicken. However, Se intervention mitigated the aforementioned alterations caused by Pb. In conclusion, Pb led to oxidative stress, which triggered heat shock response and autophagy; Se administration mitigated reproductive toxicity of Pb through strengthening antioxidant defense in the spermatogonia and Leydig cell of chicken.


Assuntos
Antioxidantes/farmacologia , Chumbo/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Selênio/farmacologia , Espermatogônias/fisiologia , Animais , Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Catalase/metabolismo , Galinhas/metabolismo , Poluentes Ambientais/metabolismo , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/metabolismo , Chumbo/metabolismo , Células Intersticiais do Testículo/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espermatogônias/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-32976987

RESUMO

Combined exposure to dietary nutrients and environmental chemicals may elicit significantly different physiological effects than single exposures. Exposure to dietary saturated fats and environmental toxins is a physiologically-significant dual exposure that is particularly associated with lower socioeconomic status, potentially placing these individuals at heightened risk of xenobiotic toxicities. However, no prior studies have examined interactions between specific lipids and environmental xenobiotics in modulating cellular health. Using primary mouse embryonic fibroblasts, we have discovered that prior exposure to the saturated fatty acid, palmitate, exacerbates cellular toxicity associated with the industrial plasticizer, bisphenol A (BPA). Cell death upon BPA exposure following palmitate pre-treatment was greater than that occurring with either exposure alone. Mechanistically, cell death was preceded by increased endoplasmic reticulum stress and loss of mitochondrial membrane potential in palmitate plus BPA exposed cells, leading to increased caspase-3 cleavage and subsequent apoptosis. Interestingly, inclusion of the unsaturated fatty acid, oleate, along with palmitate during the pre-treatment period completely abrogated the ER stress, mitochondrial toxicity, and cell death induced by subsequent exposure to BPA. Thus, our data identify for the first time an important interaction between a fatty acid and an environmental toxin and have implications for developing nutritional interventions to mitigate the deleterious effects of such xenobiotic exposures.


Assuntos
Compostos Benzidrílicos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ácido Palmítico/farmacologia , Fenóis/farmacologia , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Embrião de Mamíferos , Estresse do Retículo Endoplasmático/genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/genética , Mitocôndrias/metabolismo , Ácido Oleico/farmacologia , Cultura Primária de Células , Soroalbumina Bovina/farmacologia , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
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