Dataset Information

The day/night proteome in the murine heart.

ABSTRACT: Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ?7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.

SUBMITTER: Podobed P

PROVIDER: S-EPMC4101618 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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The day/night proteome in the murine heart.

Podobed Peter P Pyle W Glen WG Ackloo Suzanne S Alibhai Faisal J FJ Tsimakouridze Elena V EV Ratcliffe William F WF Mackay Allison A Simpson Jeremy J Wright David C DC Kirby Gordon M GM Young Martin E ME Martino Tami A TA

American journal of physiology. Regulatory, integrative and comparative physiology 20140701 2

Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimension ...[more]

PMID: 24789993

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Project description:The cerebellum harbors a circadian clock that can be shifted by scheduled mealtime and participates in behavioral anticipation of food access. Large-scale two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry was used to identify day-night variations in the cerebellar proteome of mice fed either during daytime or nighttime. Experimental conditions led to modified expression of 89 cerebellar proteins contained in 63 protein spots. Five and 33 spots were changed respectively by time-of-day or feeding conditions. Strikingly, several proteins of the heat-shock protein family (i.e., Hsp90aa1, 90ab1, 90b1, and Hspa2, 4, 5, 8, 9) were down-regulated in the cerebellum of daytime food-restricted mice. This was also the case for brain fatty acid protein (Fabp7) and enzymes involved in oxidative phosphorylation (Ndufs1) or folate metabolism (Aldh1l1). In contrast, aldolase C (Aldoc or zebrin II) and pyruvate carboxylase (Pc), two enzymes involved in carbohydrate metabolism, and vesicle-fusing ATPase (Nsf) were up-regulated during daytime restricted feeding, possibly reflecting increased neuronal activity. Significant feeding × time-of-day interactions were found for changes in the intensity of 20 spots. Guanine nucleotide-binding protein G(o) subunit alpha (Gnao1) was more expressed in the cerebellum before food access. Neuronal calcium-sensor proteins [i.e., parvalbumin (Pvalb) and visinin-like protein 1 (Vsnl1)] were inversely regulated in daytime food-restricted mice, compared to control mice fed at night. Furthermore, expression of three enzymes modulating the circadian clockwork, namely heterogeneous nuclear ribonucleoprotein K (Hnrnpk), serine/threonine-protein phosphatases 1 (Ppp1cc and Ppp1cb subunits) and 5 (Ppp5), was differentially altered by daytime restricted feeding. Besides cerebellar proteins affected only by feeding conditions or daily cues, specific changes in in protein abundance before food access may be related to behavioral anticipation of food access and/or feeding-induced shift of the cerebellar clockwork.

Project description:BackgroundNocturnal symptoms in Parkinson's disease are often treated after management of daytime manifestations. In order to better understand the unmet needs of nocturnal symptoms management, we analyzed the characteristics and burden of nocturnal symptoms from patients' perspectives and explored their changes over time. Overall symptoms (occurring at day or night) were collected to compare whether the unmet needs related to nocturnal symptoms and to overall symptoms are different.MethodsWe used a Social Listening big-data technique to analyze large amounts of Parkinson's disease symptoms in dialogues available from social media platforms in 2016 to 2018. These symptoms were classified as either overall symptoms or nocturnal symptoms. We used share of voice (SOV) of symptoms as a proportion of total dialogues per year to reflect the characteristics of symptoms. Negative sentiment score of symptoms was analyzed to find out their related burden.ResultsWe found the SOV for overall motor symptoms was 79% and had not increased between 2016 and 2018 (79%, p = 0.5). The SOV for non-motor symptoms was 69% and had grown by 7% in 2018 (p < 0.01). The SOV for motor complications was 9% and had increased by 6% in 2018 (p < 0.01). The SOV of motor symptoms was larger than non-motor symptoms and motor complications (p < 0.01). The SOV of non-motor symptoms was larger than motor complications (p < 0.01). For nocturnal symptoms, 45% of the analyzed PD population reported nocturnal symptoms in 2018, growing by 6% (p < 0.01). The SOV for nocturnal-occurring motor symptoms was higher than most non-motor symptoms. However, non-motor symptoms had the higher increases and evoked higher negative sentiment regardless of whether they occurred during the day or night. For symptoms that can occur at either day or night, each nocturnal symptom was rated with a higher negative sentiment score than the same symptom during the day.ConclusionsThe growing SOV and the greater negative sentiment of nocturnal symptoms suggest management of nocturnal symptoms is an unmet need of patients. A greater emphasis on detecting and treating nocturnal symptoms with 24-h care is encouraged.

Dataset Information

The day/night proteome in the murine heart.

Publications

The day/night proteome in the murine heart.

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