RESUMO
We investigated the influence of different fluid resuscitation techniques on the number of myeloid-derived suppressor cells (MDSCs) in rats. Seventy-two healthy Sprague-Dawley rats were randomly divided into groups that received sham operation (Sham group), hypertonic saline (HRS group), lactated ringer's solution (LRS group), or crystalloid solution (LCRS group). Six rats from each group were sacrificed by cervical dislocation at 12, 24, and 48 h after resuscitation. The spleens were harvested under sterile conditions and spleen cell suspension was prepared. The number of MDSCs was detected using flow cytometry. The number of MDSCs in the Sham group did not differ significantly among the different time points. Compared with the Sham group, the number of MDSCs after the use of the different fluid resuscitation techniques increased to varying extents and the differences among the groups were significant. The number of MDSCs in the HRS group was much lower than that of the LRS and LCRS groups at both 24 and 48 h (P < 0.05). At 12 h, the number of MDSCs in the HRS group was significantly lower than that of the LRS group (P < 0.05). The differences between the HRS and LCRS groups were not statistically significant. Shortly after hemorrhagic shock resuscitation, the immune function of rats was suppressed to a varying extent and was gradually restored over time. Resuscitation with HRS alleviated the immunosuppression at the early stage after shock.
Assuntos
Soluções Isotônicas/efeitos adversos , Células Supressoras Mieloides/efeitos dos fármacos , Soluções para Reidratação/efeitos adversos , Ressuscitação/métodos , Solução Salina Hipertônica/efeitos adversos , Animais , Soluções Cristaloides , Ratos , Ratos Sprague-Dawley , Ressuscitação/efeitos adversos , Lactato de Ringer , Baço/citologia , Baço/efeitos dos fármacosRESUMO
The aim of this study was to identify potential markers of atherosclerosis development in familial hypercholesterolemia (FH) patients. GSE13985 microarray data, generated using blood samples from 5 FH patients and 5 matched controls, was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) between FH and controls were identified and a protein-protein interaction (PPI) network was constructed. Module and hub proteins were screened in this network. The module genes were subjected to a gene ontology (GO) analysis, and a Kyoto Encyclopedia of Genes and Genomes enrichment analysis was also performed. A total of 394 genes, including 125 up- and 269 down-regulated genes, were differentially expressed. Ribosomal proteins L9 (RPL9), L35 (RPL35), and S7 (RPS7) were designated as hub nodes in the PPI network. The DEGs were found to be significantly enriched in ribosomal and oxidative phosphorylation pathways. Ribosomal protein genes were found to be involved in the ribosomal pathway. The cytochrome-c oxidase (COX) genes COX subunit VIIa polypeptide 2 (COX7A2), COX subunit VIIb (COX7B), COX subunit VIIc (COX7C), and COX subunit VIc (COX6C) were enriched in the oxidative phosphorylation pathway. Module analysis and GO enrichment analysis identified ribosomal proteins as important regulators of FH. Ribosomal and oxidative phosphorylation pathways may be closely associated with atherosclerosis development. Ribosomal protein genes and cytochrome-coxidase genes may be potential therapeutic targets for atherosclerosis.
Assuntos
Aterosclerose/genética , Redes Reguladoras de Genes , Hipercolesterolemia/genética , Mapas de Interação de Proteínas , Aterosclerose/complicações , Estudos de Casos e Controles , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Hipercolesterolemia/complicações , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismoRESUMO
Porcine circovirus type 2 (PCV2) is considered to be the main pathogen in PC-associated diseases, and significantly affects the global pig-producing industry. PCV2 continuously evolves by point mutations and genome recombinations. In the present study, we aimed to further identify recombinant PCV2 strains. We used polymerase chain reaction to detect PCV2 in the carcasses of pigs with suspected infections from different regions of Guangdong Province in China. DNA was extracted from samples with confirmed infection and full- genome amplification, sequencing, phylogenetic tree construction, gene recombination detection, and sequence alignment were performed in gene recombination analysis. Our results show that recombination occurred between the strains SHC (DQ104421) and ZhuJi2003 (AY579893). The recombination resulted in three recombinants: GD003 (KM503044), GD005 (KM487708), and GD008 (KM487709). Further analyses revealed that these novel recombinants appeared to result from recombination between the PCV2a and PCV2b strains, with crossover regions located in ORF2. This study was a comprehensive analysis that used several different methods, which demonstrated that a cluster of PCV2 strains resulted from the same type of inter-genotypic recombination pattern, with a breakpoint in the structural protein coding region. The results of our study provide both information on the recombination mechanism and disease pathogenesis and useful data for the prevention of PCV2 in the swine industry.
Assuntos
Infecções por Circoviridae/virologia , Circovirus/genética , DNA Viral/genética , Vírus Reordenados/genética , Recombinação Genética , Animais , Sequência de Bases , Linhagem Celular , Infecções por Circoviridae/patologia , Circovirus/classificação , Circovirus/patogenicidade , Células Epiteliais/patologia , Células Epiteliais/virologia , Linfonodos/patologia , Linfonodos/virologia , Dados de Sequência Molecular , Filogenia , Vírus Reordenados/patogenicidade , Alinhamento de Sequência , Baço/patologia , Baço/virologia , SuínosRESUMO
Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This non-randomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10(6) cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4- and CD8- positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Fator de Crescimento de Hepatócito/genética , Transplante de Células-Tronco Mesenquimais , Fibrose Pulmonar/terapia , Silicose/terapia , Administração Intravenosa , Adulto , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Relação CD4-CD8 , Feminino , Seguimentos , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Fator de Crescimento de Hepatócito/imunologia , Humanos , Imunoglobulina G/sangue , Pulmão/imunologia , Pulmão/patologia , Subpopulações de Linfócitos/citologia , Subpopulações de Linfócitos/imunologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Fibrose Pulmonar/sangue , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Testes de Função Respiratória , Silicose/sangue , Silicose/imunologia , Silicose/patologia , Transfecção , Transplante Autólogo , Resultado do TratamentoRESUMO
We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.
Assuntos
Animais , Feminino , Masculino , Camundongos , Gravidez , Aberrações Cromossômicas/estatística & dados numéricos , Técnicas de Cultura Embrionária , Impressão Genômica , Doenças Placentárias/genética , Placenta/metabolismo , Técnicas de Reprodução Assistida/efeitos adversos , Blastocisto/citologia , Aberrações Cromossômicas/embriologia , Embrião de Mamíferos , Epigênese Genética , Técnicas de Cultura Embrionária/estatística & dados numéricos , Incidência , Doenças Placentárias/patologia , Placenta/patologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Processos EstocásticosRESUMO
Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM) patients. We investigated whether circulating endothelial progenitor cells (cEPCs) could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16), common responders (n=12), and non-responders (n=18). There were no significant differences among these groups at baseline day 1 (P>0.05). cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/µL) vs day 1 (8.4±2.9 cEPCs/µL) in good responders (P>0.05). In contrast, cEPC levels increased significantly in the other two groups (P<0.05). SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.
Assuntos
Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Células Progenitoras Endoteliais , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.
Assuntos
Proteínas de Transporte/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Mutação , Proteínas Nucleares/genética , Adulto , Biópsia por Agulha , Medula Óssea/patologia , Análise Mutacional de DNA , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Receptores de Fator Estimulador de Colônias/genéticaRESUMO
We examined the relationship between the liver X receptor a gene (LXRα) rsl2221497 polymorphism and the susceptibility to ischemic stroke in a Chinese population. The polymerase chain reaction-restriction fragment length polymorphism technique was used to detect the genotype of rsl2221497 in the LXRαgene of 300 stroke patients and 300 healthy control subjects. The chi-square test was used to analyze the genotype distribution between the 2 groups. We found that the risk of stroke in carriers with the AA + GA genotype was 2.12-fold higher than that in GG genotype carriers (odds ratio = 2.12, 95% confidence interval: 1.58-2.99, P < 0.05). The risk of stroke in carriers of the A allele increased by 1.03-fold compared to that in G allele carriers (odds ratio = 2.03, 95% confidence interval: 1.44-3.01, P < 0.01). After adjusting for other confounding factors such smoking, hypertension, and diabetes, the A allele was found to be an independent risk factor for stroke. Therefore, the rsl2221497 polymorphism in the LXRαgene was associated with the susceptibility to stroke in a Chinese population.
Assuntos
Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Receptores Nucleares Órfãos/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Alelos , Estudos de Casos e Controles , Demografia , Frequência do Gene/genética , Humanos , Receptores X do Fígado , Modelos Logísticos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor-2α (HIF-2α) plays an essential role in oxygen homeostasis. Expression of HIF-2α-inducible genes is associated with tumor progression. In this study, we investigated this correlation immunohistochemically and using quantitative reverse transcription-polymerase chain reaction to examine various clinical and pathological features in 55 specimens of gastric cancer and 40 specimens of normal gastric tissue. The HIF-2α mRNA expression level and protein expression were significantly higher in gastric cancer tissue samples than in adjacent tissue samples. The positive rates of HIF-2α, matrix metalloprotease-9 (MMP-9), and vascular endothelial growth factor (VEGF) protein were 63.6% (35/55), 80.0% (44/55), and 65.5% (36/55) in gastric cancer tissue specimens, respectively. These values were significantly higher than those in normal gastric tissue samples (P = 0.001, P = 0.000, and P = 0.007, respectively). HIF-2α and MMP-9 were significantly correlated with primary tumor size (P = 0.0065 and P = 0.036, respectively) and invasion depth (P = 0.012 and P = 0.008, respectively). HIF-2α and VEGF were significantly correlated with lymph node involvement (P = 0.030 and P = 0.016, respectively). Expression of HIF-2α was positively correlated with the expression of VEGF and MMP-9 (P = 0.036 and P = 0.000, respectively). These results suggest that HIF-2α is involved in gastric carcinogenesis and disease progression and is a potential therapeutic target for gastric carcinoma.
Assuntos
Adenocarcinoma/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Homeostase , Humanos , Imuno-Histoquímica , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.
Assuntos
Adulto , Feminino , Humanos , Masculino , Esgotamento Profissional/genética , Doenças em Gêmeos/genética , Local de Trabalho , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/etiologia , Esgotamento Profissional/psicologia , Demografia , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/etiologia , Doenças em Gêmeos/psicologia , Interação Gene-Ambiente , Sistema de Registros , Fatores de Risco , Inquéritos e Questionários , Suécia/epidemiologiaRESUMO
This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.
Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Umbeliferonas/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Distribuição AleatóriaRESUMO
High glycine-tyrosine proteins (HGTPs), also known as keratin-associated proteins (KAPs), play a key role in the major structures and mechanical properties of wool fiber. Sheep HGTPs consist of three multigene families: KAP6, KAP7, and KAP8 genes. Polymorphisms of these three genes have been proposed to have important effects on wool fiber traits. The aim of the present study was to identify polymorphisms of the KAP6, KAP7, and KAP8 genes in four sheep breeds, including Chinese Merino superfine wool sheep, Hu sheep, a Merino x Hu crossed breed, and Romney sheep. Polymerase chain reaction (PCR) product direct sequencing, PCR-single-strand conformation polymorphism, and cloned sequencing methods were used to find genetic variation and identify polymorphisms in these genes. The Mutation Surveyor v3.97 software was used to analyze the sequences. These methods revealed six different sequences of the KAP6 gene, two different sequences of the KAP7 gene, and five different sequences of the KAP8 gene. Accordingly, three (with frequencies>1%) single nucleotide polymorphisms (SNPs) of the KAP6 gene, one SNP of the KAP7 gene, and five SNPs of the KAP8 gene were detected. Interestingly, some of these sequences were present in only certain sheep breeds, thereby suggesting that these special allele sequences could be used as candidate genes of wool characteristics in further studies.
Assuntos
Queratinas/genética , Carneiro Doméstico/genética , Alelos , Animais , Cruzamento , Polimorfismo de Nucleotídeo Único , Lã/metabolismoRESUMO
Malignant cells show increased invasion potency in vitro and in vivo. This process is considered to be mediated by matrix-metalloproteases (MMPs). Hypoxia-inducible factor-2α (HIF-2α) may upregulate MMP-2 expression; however, little is known about the correlation between HIF-2α and MMP-2 expressions in breast cancer. The current study investigated this correlation immunohistochemically according to various clinical and pathological features in 102 paraffin-embedded archival tissue block specimens from patients with breast cancer. HIF-2α and MMP-2 expression was detected in 60.8% (62/102) and 65.7% (67/102) of tumor samples, respectively. HIF-2α expression was significantly correlated with tumor size (P = 0.019), lymph node involvement (P = 0.035), and metastasis (P = 0.035). MMP-2 expression was significantly associated with lymph node involvement (P = 0.043) and metastasis (P = 0.003). Univariate analyses revealed that HIF-2α (P = 0.001) and MMP-2 (P = 0.000) expressions were significantly associated with a poorer survival rate, as well as tumor size, lymph node invasion, and distant metastasis. Multivariate analysis revealed that HIF-2α (P = 0.003) and the T-stage (P = 0.000) were independent prognostic factors of overall survival. Spearman correlation analysis revealed that HIF-2α and MMP-2 expressions were significantly correlated (r = 0.990; P = 0.041). These results suggest that high HIF- 2α expression is associated with poor overall survival in patients with breast cancer, indicating that HIF-2α could be a valuable marker of breast cancer progression.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Metaloproteinase 2 da Matriz/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/patologia , Metaloproteinase 2 da Matriz/genética , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
A recently developed revolutionary approach to transcriptomics, RNA-Seq, and suppression subtractive hybridization are powerful tools for gene expression research. However, currently, the difficulty of isolating high-quality RNAs from plant tissues bearing abundant complex polysaccharides, polyphenolics, and secondary metabolites is a serious problem that not only limits the application of these technologies but also hinders studies dealing with RNA in general. We have developed a consistent protocol to prepare highly intact and pure RNAs from tissues of a variety of field-grown plant species, with high yields, in 2 to 3 h. Additionally, this method can be readily applied to mammalian, yeast, and bacterial cells.
Assuntos
RNA de Plantas/isolamento & purificação , Fracionamento Celular/métodos , Fracionamento Químico/métodos , Hibridização de Ácido Nucleico , Células Vegetais/química , RNA de Plantas/química , RNA de Plantas/normas , Análise de Sequência de RNARESUMO
We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.
Assuntos
Animais , Masculino , Camundongos , Envelhecimento/sangue , Apolipoproteína A-II/sangue , Autoanticorpos/sangue , Estresse Oxidativo/genética , alfa-Fetoproteínas/metabolismo , Envelhecimento/genética , Apolipoproteína A-II/genética , Autoanticorpos/genética , Biomarcadores/sangue , Biomarcadores/metabolismo , Oxirredução , Proteômica , Baço/citologia , alfa-Fetoproteínas/genéticaRESUMO
We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2â m, -6â m, -12â m, -15â m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12â m sera. Two proteins decreased in the sera from SAMP8-2â m, -6â m, and -12â m mice, and divided into 2 spots each in SAMP8-15â m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2â m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.