检索结果-南通市图书馆

Cytokine and Antioxidant Regulation in the Intestine of the Gray Mouse Lemur (Microcebus murinus) During Torpor

Genomics, Proteomics & Bioinformatics 2015年第2期13卷 127-135页

作者： Shannon N.Tessier Barbara A.Katzenback fabien pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry & Department of Biology Carleton University Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School Department of Biology University of Waterloo UMR 7179 Centre National de la Recherche Scientifique Muse'um National d'Histoire Naturelle

During food shortages, the gray mouse lemur（Microcebus murinus） of Madagascar experiences daily torpor thereby reducing energy expenditures. The present study aimed to understand the impacts of torpor on the immune system and antioxidant response in the gut of these *** interaction may be of critical importance given the trade-off between the energetically costly immune response and the need to defend against pathogen entry during hypometabolism. The protein levels of cytokines and antioxidants were measured in the small intestine（duodenum, jejunum,and ileum） and large intestine of aroused and torpid lemurs. While there was a significant decrease of some pro-inflammatory cytokines（IL-6 and TNF-a） in the duodenum and jejunum during torpor as compared to aroused animals, there was no change in anti-inflammatory cytokines. We observed decreased levels of cytokines（IL-12p70 and M-CSF）, and several chemokines（MCP-1and MIP-2） but an increase in MIP-1a in the jejunum of the torpid animals. In addition, we evaluated antioxidant response by examining the protein levels of antioxidant enzymes and total antioxidant capacity provided by metabolites such as glutathione（and others）. Our results indicatedthat levels of antioxidant enzymes did not change between torpor and aroused states, although antioxidant capacity was significantly higher in the ileum during torpor. These data suggest a suppression of the immune response, likely as an energy conservation measure, and a limited role of antioxidant defenses in supporting torpor in lemur intestine.

关键词： Primate torpor Cytokines Chemokines Antioxidant enzymes Gut immunology

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Regulation of the PI3K/AKT Pathway and Fuel Utilization During Primate Torpor in the Gray Mouse Lemur, Microcebus murinus

引用

Genomics, Proteomics & Bioinformatics 2015年第2期13卷 91-102页

作者： Shannon N.Tessier Jing Zhang Kyle K.Biggar Cheng-Wei Wu fabien pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry & Department of Biology Carleton University Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School Chemistry and Chemical Engineering Department Royal Military College of Canada Biochemistry Department Schulich School of Medicine and Dentistry Western University Department of Biology Genetics Institute University of Florida UMR 7179 Centre National de la Recherche Scientifique Muse'um National d'Histoire Naturelle

Gray mouse lemurs（Microcebus murinus） from Madagascar present an excellent model for studies of torpor regulation in a primate species. In the present study, we analyzed the response of the insulin signaling pathway as well as controls on carbohydrate sparing in six different tissues of torpid versus aroused gray mouse lemurs. We found that the relative level of phospho-insulin receptor substrate（IRS-1） was significantly increased in muscle, whereas the level of phospho-insulin receptor（IR） was decreased in white adipose tissue（WAT） of torpid animals, both suggesting an inhibition of insulin/insulin-like growth factor-1（IGF-1） signaling during torpor in these tissues. By contrast, the level of phospho-IR was increased in the liver. Interestingly, muscle,WAT, and liver occupy central roles in whole body homeostasis and each displays regulatory controls operating at the plasma membrane. Changes in other tissues included an increase in phosphoglycogen synthase kinase 3a（GSK3a） and decrease in phospho-ribosomal protein S6（RPS6） in the heart, and a decrease in phospho-mammalian target of rapamycin（m TOR） in the kidney. Pyruvate dehydrogenase（PDH） that gates carbohydrate entry into mitochondria is inhibited via phosphorylation by pyruvate dehydrogenase kinase（e.g., PDK4）. In the skeletal muscle, the protein expression of PDK4 and phosphorylated PDH at Ser 300 was increased, suggesting inhibition during torpor. In contrast, there were no changes in levels of PDH expression and phosphorylation in other tissues comparing torpid and aroused animals. Information gained from these studies highlight the molecular controls that help to regulate metabolic rate depression and balance energetics during primate torpor.

关键词： Insulin signaling pathway PI3K/AKT m TOR GSK3 Pyruvate dehydrogenase Metabolic rate depression

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Induction of Antioxidant and Heat Shock Protein Responses During Torpor in the Gray Mouse Lemur, Microcebus murinus

引用

Genomics, Proteomics & Bioinformatics 2015年第2期13卷 119-126页

作者： Cheng-Wei Wu Kyle K.Biggar Jing Zhang Shannon N.Tessier fabien pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry & Department of Biology Carleton University Department of Biology Genetics Institute University of Florida Biochemistry Department Schulich School of Medicine and Dentistry Western University Chemistry and Chemical Engineering Department Royal Military College Of Canada Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School UMR 7179 Centre National de la Recherche Scientifique Muse'um National d'Histoire Naturelle

A natural tolerance of various environmental stresses is typically supported by various cytoprotective mechanisms that protect macromolecules and promote extended viability. Among these are antioxidant defenses that help to limit damage from reactive oxygen species and chaperones that help to minimize protein misfolding or unfolding under stress conditions. To understand the molecular mechanisms that act to protect cells during primate torpor, the present study characterizes antioxidant and heat shock protein（HSP） responses in various organs of control（aroused）and torpid gray mouse lemurs, Microcebus murinus. Protein expression of HSP70 and HSP90 a was elevated to 1.26 and 1.49 fold, respectively, in brown adipose tissue during torpor as compared with control animals, whereas HSP60 in liver of torpid animals was 1.15 fold of that in control（P 〈 0.05）. Among antioxidant enzymes, protein levels of thioredoxin 1 were elevated to 2.19 fold in white adipose tissue during torpor, whereas Cu–Zn superoxide dismutase 1 levels rose to 1.1 fold in skeletal muscle（P 〈 0.05）. Additionally, total antioxidant capacity was increased to 1.6 fold in liver during torpor（P 〈 0.05）, while remaining unchanged in the five other tissues. Overall, our data suggest that antioxidant and HSP responses are modified in a tissue-specific manner during daily torpor in gray mouse lemurs. Furthermore, our data also show that cytoprotective strategies employed during primate torpor are distinct from the strategies in rodent hibernation as reported in previous studies.

关键词： Heat shock proteins Antioxidant capacity Primate hypometabolism Stress response

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Modulation of Gene Expression in Key Survival Pathways During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus

引用

Genomics, Proteomics & Bioinformatics 2015年第2期13卷 111-118页

作者： Kyle K.Biggar Cheng-Wei Wu Shannon N.Tessier Jing Zhang fabien pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry & Department of Biology Carleton University Biochemistry Department Schulich School of Medicine and Dentistry Western University Department of Biology Genetics Institute University of Florida Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School Chemistry and Chemical Engineering Department Royal Military College of Canada UMR 7179 Centre National de la Recherche Scientifique Muse'um National d'Histoire Naturelle

A variety of mammals employ torpor as an energy-saving strategy in environments of marginal or severe stress either on a daily basis during their inactive period or on a seasonal basis during prolonged multi-day hibernation. Recently, a few Madagascar lemur species have been identified as the only primates that exhibit torpor; one of these is the gray mouse lemur（Microcebus murinus）. To explore the regulatory mechanisms that underlie daily torpor in a primate, we analyzed the expression of 28 selected genes that represent crucial survival pathways known to be involved in squirrel and bat hibernation. Array-based real-time PCR was used to compare gene expression in control（aroused） versus torpid lemurs in five tissues including the liver, kidney,skeletal muscle, heart, and brown adipose tissue. Significant differences in gene expression during torpor were revealed among genes involved in glycolysis, fatty acid metabolism, antioxidant defense, apoptosis, hypoxia signaling, and protein protection. The results showed upregulation of select genes primarily in liver and brown adipose tissue. For instance, both tissues showed elevated gene expression of peroxisome proliferator activated receptor gamma（ppargc）, ferritin（fth1）, and protein chaperones during torpor. Overall, the data show that the expression of only a few genes changed during lemur daily torpor, as compared with the broader expression changes reported for hibernation in ground squirrels. These results provide an indication that the alterations in gene expression required for torpor in lemurs are not as extensive as those needed for winter hibernation in squirrel models. However, identification of crucial genes with altered expression that support lemur torpor provides key targets to be explored and manipulated toward a goal of translational applications of inducible torpor as a treatment option in human biomedicine.

关键词： Daily torpor Primate hypometabolism PPAR gamma coactivator Ferritin Chaperone proteins

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Regulation of Torpor in the Gray Mouse Lemur:Transcriptional and Translational Controls and Role of AMPK Signaling

引用

Genomics, Proteomics & Bioinformatics 2015年第2期13卷 103-110页

作者： Jing Zhang Shannon N.Tessier Kyle K.Biggar Cheng-Wei Wu fabien pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry & Department of Biology Carleton University Chemistry and Chemical Engineering Department Royal Military College of Canada Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School Biochemistry Department Schulich School of Medicine and Dentistry Western University Department of Biology Genetics Institute University of Florida UMR 7179 Centre National de la Recherche Scientifique Muse'um National d'Histoire Naturelle

The gray mouse lemur（Microcebus murinus） is one of few primate species that is able to enter daily torpor or prolonged hibernation in response to environmental stresses. With an emerging significance to human health research, lemurs present an optimal model for exploring molecular adaptations that regulate primate hypometabolism. A fundamental challenge is how to effectively regulate energy expensive cellular processes（e.g., transcription and translation） during transitionsto/from torpor without disrupting cellular homeostasis. One such regulatory mechanism is reversible posttranslational modification of selected protein targets that offers fine cellular control without the energetic burden. This study investigates the role of phosphorylation and/or acetylation in regulating key factors involved in energy homeostasis（AMP-activated protein kinase, or AMPK, signaling pathway）, m RNA translation（eukaryotic initiation factor 2a or e IF2 a, eukaryotic initiation factor 4E or e IF4 E, and initiation factor 4E binding protein or 4EBP）, and gene transcription（histone H3） in six tissues of torpid and aroused gray mouse lemurs. Our results indicated selective tissue-specific changes of these regulatory proteins. The relative level of Thr172-phosphorylated AMPKa was significantly elevated in the heart but reduced in brown adipose tissue during daily torpor, as compared to the aroused lemurs, implicating the regulation of AMPK activity during daily torpor in these tissues. Interestingly, the levels of the phosphorylated e IFs were largely unaltered between aroused and torpid animals. Phosphorylation and acetylation of histone H3 were examined as a marker for transcriptional regulation. Compared to the aroused lemurs, level of Ser10-phosphorylated histone H3 decreased significantly in white adipose tissue during torpor, suggesting global suppression of gene transcription. However, a significant increase in acetyl-histone H3 in the heart of torpid lemurs indicated a possible stim

关键词： Posttranslational modification Histone H3 Ribosomal initiation factorsMetabolic rate depression AMP-activated protein kinase

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Primate Torpor: Regulation of Stress-activated Protein Kinases During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus

引用

Genomics, Proteomics & Bioinformatics 2015年第2期13卷 81-90页

作者： Kyle K.Biggar Cheng-Wei Wu Shannon N.Tessier Jing Zhang fabien pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry and Department of Biology Carleton University Biochemistry Department Schulich School of Medicine and Dentistry Western University Department of Biology Genetics Institute University of Florida Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School Chemistry and Chemical Engineering Department Royal Military College of Canada UMR 7179 Centre National de la Recherche Scientifique Muse'um National d0Histoire Naturelle

Very few selected species of primates are known to be capable of entering torpor. This exciting discovery means that the ability to enter a natural state of dormancy is an ancestral trait among primates and, in phylogenetic terms, is very close to the human lineage. To explore the regulatory mechanisms that underlie primate torpor, we analyzed signal transduction cascades to discover those involved in coordinating tissue responses during torpor. The responses of mitogen-activated protein kinase（MAPK） family members to primate torpor were compared in six organs of control（aroused） versus torpid gray mouse lemurs, Microcebus murinus. The proteins examined include extracellular signal-regulated kinases（ERKs）, c-jun NH2-terminal kinases（JNKs）, MAPK kinase（MEK）, and p38, in addition to stress-related proteins p53 and heat shock protein 27（HSP27）. The activation of specific MAPK signal transduction pathways may provide a mechanism to regulate the expression of torpor-responsive genes or the regulation of selected downstream cellular processes. In response to torpor, each MAPK subfamily responded differently during torpor and each showed organ-specific patterns of response. For example, skeletal muscle displayed elevated relative phosphorylation of ERK1/2 during torpor. Interestingly, adipose tissues showed the highest degree of MAPK activation. Brown adipose tissue displayed an activation of ERK1/2 and p38, whereas white adipose tissue showed activation of ERK1/2, p38, MEK, and JNK during torpor. Importantly, both adipose tissues possess specialized functions that are critical for torpor, with brown adipose required for non-shivering thermogenesis and white adipose utilized as the primary source of lipid fuel for torpor. Overall, these data indicate crucial roles of MAPKs in the regulation of primate organs during torpor.

关键词： Metabolic rate depression Signal transduction Mitogen activated protein kinase

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：