The regulation of troponins I, C and ANP by GATA4 and NKX2-5 in heart of hibernating thirteen-Lined ground squirrels, ictidomys tridecemlineatus

Luu, Bryan E.; Tessier, Shannon N.; Storey, Kenneth B.

doi:10.1016/j.cryobiol.2017.12.068

Cited by 6 publications

(7 citation statements)

References 39 publications

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“…In contrast, hibernation results in a decrease in most novel microRNA within the heart and skeletal muscle, which is also observed for known microRNA [17]. A number of studies have shown that hibernating I. tridecemlineatus regulate select muscle-specific transcription factors which would facilitate remodeling of the heart and skeletal muscle [26][27][28]. The observed decrease in novel microRNA may play a role in the bigger picture of molecular signaling by which muscle remodeling occurs in the heart and skeletal tissues of hibernators.…”

Section: Discussionmentioning

confidence: 77%

Torpor‐responsive expression of novel microRNA regulating metabolism and other cellular pathways in the thirteen‐lined ground squirrel, Ictidomys tridecemlineatus

Luu

Biggar

et al. 2016

FEBS Letters

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Research has demonstrated the importance of microRNA in cold-tolerant animals, including their dynamic regulation throughout mammalian hibernation. In this study, we used small RNA sequencing and bioinformatic methods to identify novel microRNA regulating gene expression during hibernation in thirteen-lined ground squirrels, Ictidomys tridecemlineatus. A group of 17 novel microRNA was identified, and their relative expression was quantitated using real-time quantitative polymerase chain reaction in liver, skeletal muscle, and heart tissues over four experimental conditions that represent the torpor-arousal cycle. Predicted mRNA targets of these novel microRNA were found to be enriched in biological processes known to be regulated during hibernation, such as lipid metabolism, ion-transport ATPases, and various cellular signaling cascades. This study provides an analysis of several novel microRNA that may be crucial to adaptation during hibernation.

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Section: Discussionmentioning

confidence: 77%

Torpor‐responsive expression of novel microRNA regulating metabolism and other cellular pathways in the thirteen‐lined ground squirrel, Ictidomys tridecemlineatus

Luu

Biggar

et al. 2016

FEBS Letters

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“…Among the protein biomarkers approved by regulatory agencies as FDA are carcinoembryonic antigen (CAE), thyroglobulin (Tg), and prostate-specific antigen (PSA), which monitor the progression of colon, thyroid, and breast cancer, respectively [1]. Moreover, troponin T, troponin I, and creatine kinase (CK) have been used to diagnose acute myocardial infarction, myocardial injury, and myocardial necrosis [2,3], and brain natriuretic peptide (BNP) has been employed as an indicator of congestive heart failure and acute coronary syndrome diagnosis [4].…”

Section: Introductionmentioning

confidence: 99%

A Selected Reaction Monitoring Mass Spectrometry Protocol for Validation of Proteomic Biomarker Candidates in Studies of Psychiatric Disorders

Reis‐de‐Oliveira

Garcia

Guest

et al. 2017

Advances in Experimental Medicine and Biology

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Most biomarker candidates arising from proteomic studies of psychiatric disorders have not progressed for use in clinical studies due to insufficient validation steps. Here we describe a selective reaction monitoring mass spectrometry (SRM-MS) approach that could be used as a follow-up validation tool of proteins identified in blood serum or plasma. This protocol specifically covers the stages of peptide selection and optimization. The increasing application of SRM-MS should enable fast, sensitive, and robust methods with the potential for use in clinical studies involving sampling of serum or plasma. Understanding the molecular mechanisms and identifying potential biomarkers for risk assessment, diagnosis, prognosis, and prediction of drug response goes toward the implementation of translational medicine strategies for improved treatment of patients with psychiatric disorders and other debilitating diseases.

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“…Despite this unified activation pattern, the phosphorylation status of the downstream transcription factors presently measured were not similarly enhanced, attesting to the capacity for MAPKs to propagate highly specific responses despite a vast range of downstream substrates. Other possible substrates for cardiac-specific MAPK regulation may include MEF2 (regulated by p38 and ERK5) and GATA4 (regulated by ERK1/2) transcription factors which have previously been shown to play an important role in the heart of thirteen-lined ground squirrels during torpor Luu et al 2014]. In these studies, GATA4 phosphorylation increased significantly during early arousal from torpor, suggesting that GATA4 may be regulated by ERK1/2 at this hibernation stage.…”

Section: Expression Of Heat Shock Proteins In Skeletal and Cardiac Mumentioning

confidence: 69%

Regulation of gene expression over cycles of torpor-arousal in thirteen-lined ground squirrels

Tessier¹

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Mammalian hibernators undergo profound behavioural, physiological and biochemical changes to cope with hypothermia, ischemia-reperfusion, and finite fuel reserves during days or weeks of continuous torpor. Against a backdrop of global suppression of energy-expensive processes such as transcription and translation, selected genes/proteins are strategically up-regulated to meet challenges associated with hibernation. Hence, hibernation involves substantial transcriptional and posttranscriptional regulatory mechanisms and provides a model to determine how a set of common genes/proteins can be differentially regulated to enhance stress tolerance beyond that which is possible for nonhibernators. The present research analyzed epigenetic factors, signal transduction pathways, transcription factors, and RNA binding proteins that regulate gene/protein expression programs that define the hibernating phenotype.Epigenetic factors alter gene expression programs by influencing the accessibility of DNA promoter regions to the transcriptional machinery. While DNA methylation was not differentially regulated comparing summer and winter animals, posttranslational modifications on histone proteins were responsive to torpor-arousal, possibly providing a mechanism to dynamically alter chromatin structure. Unique posttranslational modifications on H3 and H2B were identified by mass spectrometry; these have never been found in other organisms. Signal transduction pathways such as mitogen-activated protein kinases convert information received at the cell surface to regulatory targets within cells that promote changes in gene expression. Results showed that MAPK regulation is crucial during arousal from torpor in muscle and heart. Important cytoprotective features needed for hibernation are antioxidant defenses; regulation of antioxidant genes is under primary control of transcription factors, such as Nrf2. Data iv presented elucidates the regulation of Nrf2 transcription factors by post-translational modifications (e.g. serine phosphorylation, lysine acetylation) and protein-protein interactions with a negative regulator (KEAP1) during hibernation. Finally, a role for RNA binding proteins including TIA-1, TIAR, and PABP-1 is described. Data showed the localization of RNA-binding proteins to subnuclear structures which may represent highly organized storage centers and/or enhance mRNA stability. Taken together, the thesis identifies novel regulatory mechanisms that aid suppression of transcriptional and translational rates, while also coordinating complex pathways that selectively enhance cytoprotective pathways aimed at mitigating stresses associated with torpor-arousal. v

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The regulation of troponins I, C and ANP by GATA4 and NKX2-5 in heart of hibernating thirteen-Lined ground squirrels, ictidomys tridecemlineatus

Cited by 6 publications

References 39 publications

Torpor‐responsive expression of novel microRNA regulating metabolism and other cellular pathways in the thirteen‐lined ground squirrel, Ictidomys tridecemlineatus

Torpor‐responsive expression of novel microRNA regulating metabolism and other cellular pathways in the thirteen‐lined ground squirrel, Ictidomys tridecemlineatus

A Selected Reaction Monitoring Mass Spectrometry Protocol for Validation of Proteomic Biomarker Candidates in Studies of Psychiatric Disorders

Regulation of gene expression over cycles of torpor-arousal in thirteen-lined ground squirrels

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