title: Proteomic mechanisms of cardioprotection during mammalian hibernation in woodchucks, Marmota monax.
abstract: Mammalian hibernation is a unique strategy for winter survival in response to limited food supply and harsh climate, which includes resistance to cardiac arrhythmias. We previously found that hibernating woodchucks (Marmota monax) exhibit natural resistance to Ca2+ overload-related cardiac dysfunction and nitric oxide (NO)-dependent vasodilation, which maintains myocardial blood flow during hibernation. Since the cellular/molecular mechanisms mediating the protection are less clear, the goal of this study was to investigate changes in the heart proteome and reveal related signaling networks that are involved in establishing cardioprotection in woodchucks during hibernation. This was accomplished using isobaric tags for a relative and absolute quantification (iTRAQ) approach. The most significant changes observed in winter hibernation compared to summer non-hibernation animals were upregulation of the antioxidant catalase and inhibition of endoplasmic reticulum (ER) stress response by downregulation of GRP78, mechanisms which could be responsible for the adaptation and protection in hibernating animals. Furthermore, protein networks pertaining to NO signaling, acute phase response, CREB and NFAT transcriptional regulations, protein kinase A and α-adrenergic signaling were also dramatically upregulated during hibernation. These adaptive mechanisms in hibernators may provide new directions to protect myocardium of non-hibernating animals, especially humans, from cardiac dysfunction induced by hypothermic stress and myocardial ischemia.
authors.affiliation: Center for Advanced Proteomics Research and Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, New Jersey 07103, United States. liho2@njms.rutgers.edu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Mohit Raja
authors.initials: MR
authors.lastname: Jain
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Kudej
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
mesh_terms: D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006321:Heart / Q000502:physiology*; D006605:Hibernation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008392:Marmota / Q000502:physiology*; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D017725:Ventricular Pressure
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D020543:Proteome