title: Primate Torpor: Regulation of Stress-activated Protein Kinases During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Biochemistry Department, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Kyle K
authors.initials: KK
authors.lastname: Biggar
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Department of Biology, Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Department of Surgery & Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Tessier
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON K7K 7B4, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, 91800 Brunoy, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Pifferi
authors.affiliation: UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, 91800 Brunoy, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Perret
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada. Electronic address: kenneth_storey@carleton.ca.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Storey
mesh_terms: D002001:Adipose Tissue, Brown / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D016565:Cheirogaleidae / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D064348:Torpor
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases
keywords: Metabolic rate depression; Mitogen activated protein kinase; Signal transduction