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

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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

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

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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

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

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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

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

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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

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

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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

镧助剂对模拟生物沼气重整制备合成气中Ni/SBA-15催化剂结构和性能的影响

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物理化学学报 2009年第8期25卷 1611-1617页

作者：郎宝李秀金季生福 fabien Habimana 李成岳北京化工大学化工资源有效利用国家重点实验室北京100029 北京化工大学化学工程学院环境工程系北京100029

以介孔分子筛SBA-15为载体,采用浸渍法制备了镍质量分数(w)为12.5%,并且分别添加质量分数(w)为2.5%的镧、铈、镁、钙、锶等助剂的系列Ni基催化剂.以CH4/CO2体积比为2∶1的模拟生物沼气和适量氧气作为原料气,在常压固定床反应器上评价了... 详细信息

以介孔分子筛SBA-15为载体,采用浸渍法制备了镍质量分数(w)为12.5%,并且分别添加质量分数(w)为2.5%的镧、铈、镁、钙、锶等助剂的系列Ni基催化剂.以CH4/CO2体积比为2∶1的模拟生物沼气和适量氧气作为原料气,在常压固定床反应器上评价了催化剂对模拟生物沼气重整制合成气的反应性能.采用X射线粉末衍射(XRD)、N2吸附/脱附、透射电子显微镜(TEM)、X射线光电子能谱(XPS)及H2程序升温还原(H2-TPR)等对催化剂的结构进行了表征.催化活性评价显示,添加镧助剂的2.5%La/12.5%Ni/SBA-15催化剂比添加铈、镁、钙、锶等助剂的催化剂具有更高的催化活性,并且具有很好的稳定性.因此,文中着重研究了镧助剂对催化剂结构和模拟生物沼气重整制合成气的反应性能的影响.结果表明,镧能明显提高Ni/SBA-15催化剂的表面镍含量,同时还具有很好的抗积炭作用,在850℃的温度下反应820h没有发现积炭生成,这些可能是提高催化剂性能和稳定性的重要因素.

关键词：镍镧助剂 SBA-15 生物沼气重整合成气

Starch Metabolism in Plant and Its Applications in Food Industry

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Advances in Biological Chemistry 2023年第4期13卷 111-127页

作者： fabien Nsanzabera Evangeline Irakoze Alexis Manishimwe Aimable Mwiseneza Jean Bosco Nsengiyumva fabien Nkurikiyimana Department of Education in Sciences Faculty of Education University of Technology and Arts of Byumba (UTAB) Byumba Rwanda African Center of Excellence in Innovative Teaching and Learning Mathematics and Science (ACE-ITLMS) College of Education University of Rwanda Kayonza Rwanda

Starch, a polymer of sugars in plants, is widely used in various industries due to its properties. It is synthesized through ADP-glucose formation and enzyme-mediated processes. Starch is formed during the day and broken down into sugars at night, which are then transported and converted back to starch in storage tissues. This review explores starch metabolism pathways and its role in the food industry, providing valuable insights on energy storage in plants.

关键词： Starch Metabolism Gelatinization Retrogradation Starch Biosynthesis Starch Degradation

Laparoscopic sleeve gastrectomy and gastroesophageal reflux

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World Journal of Gastroenterology 2015年第36期21卷 10348-10357页

作者： fabien Stenard Antonio Iannelli Digestive and Oncology Unit Mutualiste Hospital Digestive Unit Archet 2 HospitalUniversity Hospital of Nice Inserm U1065Team 8 "Hepatic complications of obesity" University of Nice Sophia-Antipolis

Bariatric surgery is the only effective procedure that provides long-term sustained weight loss. Sleeve gastrectomy(SG) has emerged over the last few years to be an ideal bariatric procedure because it has several advantages compared to more complex bariatric procedures,including avoiding an intestinal bypass. However,several published follow-up studies report an increased rate of gastroesophageal reflux(GERD) after a SG. GERD is described as either de novo or as being caused by aggravation of preexisting symptoms. However,the literature on this topic is ambivalent despite the potentially increased rate of GERDs that may occur after this common bariatric procedure. This article reviews the mechanisms responsible for GERD in obese subjects as well as the results after a SG with respect to GERD. Future directions for clinical research are discussed along with the current surgical options for morbidly obese patients with GERD and undergoing bariatric surgery.

关键词： Gastroesophageal reflux Sleeve gastrectomy Morbid

Response of C and N cycles to N fertilization in Sphagnum and Molinia-dominated peat mesocosms

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Journal of Environmental Sciences 2019年第3期31卷 264-272页

作者： fabien Leroy Sébastien Gogo Christophe Guimbaud André-Jean Francez Renata Zocatelli Christian Défarge Léonard Bernard-Jannin Zhen Hu Fatima Laggoun-Défarge University of Orleans ISTO CNRS ISTO BRGM ISTO University of Orleans LPC2E CNRS LPC2E UMR CNRS 6553 ECOBIO University of Rennes 1 University of Orleans Cellule R&D CETRAHE School of Environmental Science and Engineering Shandong University

Plant communities play an important role in the C-sink function of peatlands. However,global change and local perturbations are expected to modify peatland plant communities,leading to a shift from Sphagnum mosses to vascular plants. Most studies have focused on the direct effects of modification in plant communities or of global change(such as climate warming, N fertilization) in peatlands without considering interactions between these disturbances that may alter peatlands' C function. We set up a mesocosm experiment to investigate how Greenhouse Gas(CO_2, CH_4, N_2O) fluxes, and dissolved organic carbon(DOC)and total dissolved N(TN) contents are affected by a shift from Sphagnum mosses to Molinia caerulea dominated peatlands combined with N fertilization. Increasing N deposition did not alter the C fluxes(CO_2 exchanges, CH_4 emissions) or DOC content. The lack of N effect on the C cycle seems due to the capacity of Sphagnum to efficiently immobilize N. Nevertheless, N supply increased the N_2O emissions, which were also controlled by the plant communities with the presence of Molinia caerulea reducing N_2O emissions in the Sphagnum mesocosms. Our study highlights the role of the vegetation composition on the C and N fluxes in peatlands and their responses to the N deposition. Future research should now consider the climate change in interaction to plants community modifications due to their controls of peatland sensitivity to environmental conditions.

关键词： CO2 and CH4 N2O Peatland Plant community composition Sphagnum moss Graminoid