Abstract:
:Troponin I (TnI) is a major regulator of cardiac muscle contraction and relaxation. During physiological and pathological stress, TnI is differentially phosphorylated at multiple residues through different signaling pathways to match cardiac function to demand. The combination of these TnI phosphorylations can exhibit an expected or unexpected functional integration, whereby the function of two phosphorylations are different than that predicted from the combined function of each individual phosphorylation alone. We have shown that TnI Ser-23/24 and Ser-150 phosphorylation exhibit functional integration and are simultaneously increased in response to cardiac stress. In the current study, we investigated the functional integration of TnI Ser-23/24 and Ser-150 to alter cardiac contraction. We hypothesized that Ser-23/24 and Ser-150 phosphorylation each utilize distinct molecular mechanisms to alter the TnI binding affinity within the thin filament. Mathematical modeling predicts that Ser-23/24 and Ser-150 phosphorylation affect different TnI affinities within the thin filament to distinctly alter the Ca2+-binding properties of troponin. Protein binding experiments validate this assertion by demonstrating pseudo-phosphorylated Ser-150 decreases the affinity of isolated TnI for actin, whereas Ser-23/24 pseudo-phosphorylation is not different from unphosphorylated. Thus, our data supports that TnI Ser-23/24 affects TnI-TnC binding, while Ser-150 phosphorylation alters TnI-actin binding. By measuring force development in troponin-exchanged skinned myocytes, we demonstrate that the Ca2+ sensitivity of force is directly related to the amount of phosphate present on TnI. Furthermore, we demonstrate that Ser-150 pseudo-phosphorylation blunts Ser-23/24-mediated decreased Ca2+-sensitive force development whether on the same or different TnI molecule. Therefore, TnI phosphorylations can integrate across troponins along the myofilament. These data demonstrate that TnI Ser-23/24 and Ser-150 phosphorylation regulates muscle contraction in part by modulating different TnI interactions in the thin filament and it is the combination of these differential mechanisms that provides understanding of their functional integration.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Salhi HE,Hassel NC,Siddiqui JK,Brundage EA,Ziolo MT,Janssen PM,Davis JP,Biesiadecki BJdoi
10.3389/fphys.2016.00567subject
Has Abstractpub_date
2016-12-15 00:00:00pages
567issn
1664-042Xjournal_volume
7pub_type
杂志文章abstract::Ticks and tick-borne pathogens affect health and welfare of companion animals worldwide, and some human tick-borne diseases are associated with exposure to domestic animals. Vaccines are the most environmentally friendly alternative to acaracides for the control of tick infestations, and to reduce the risk for tick-bo...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00977
更新日期:2019-07-26 00:00:00
abstract::Background: Nrg4 expression has been linked to brown adipose tissue activity and browning of white adipocytes in mice. Here, we aimed to investigate whether these observations could be translated to humans by investigating NRG4 mRNA and markers of brown/beige adipocytes in human visceral (VAT) and subcutaneous adipose...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00039
更新日期:2019-01-31 00:00:00
abstract::Lepidopteran species detect CO2 via a specialized organ located on the peripheral segment of the labial palps, the labial palp pit organ (LPO). Based on tracing of LPO sensory neurons targeting one distinct antennal-lobe glomerulus, Kent and her colleagues described the projections originating from the LPO in the sphi...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00202
更新日期:2020-03-17 00:00:00
abstract::Hypoxic exercise may represent a novel therapeutic strategy to reduce and prevent obesity through the regulation of lipid metabolism. During hypoxic exercise, the targeting of peroxisome proliferator-activated receptor gamma (PPARγ) by miR-27b has been proposed to be one of the mechanisms involved in the modulation of...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.01090
更新日期:2020-08-31 00:00:00
abstract::The effect of training status on post-exercise flow-mediated dilation (FMD) is not well characterized. We tested the hypothesis that the more trained the subjects, the lower the reduction in FMD after an acute bout of aerobic exercise. Forty-seven men (mean ± SD, age: 20.1 ± 1.2 years, body mass: 75.5 ± 5.1 kg, height...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00348
更新日期:2020-05-08 00:00:00
abstract::Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional medicines and is thought to be a tonic. It has been claimed that ginseng may improve vitality and health. Recent studies have advanced ginseng pharmacology and shown that ginseng has various pharmacological effects in the nervous system. G...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2014.00098
更新日期:2014-03-19 00:00:00
abstract::Obesity is a worldwide epidemic disease that induces important structural and functional changes to the heart and predisposes a patient to devastating cardiac complications. Sirtuin1 (SIRT1) has been found to have roles in regulating cardiac function, but whether it can help in cardioprotection is not clear. The aim o...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00103
更新日期:2020-03-11 00:00:00
abstract::The paper reports application of a Markov-like stochastic process agent-based model and a "virtual farm" concept for enhancement of site-specific Integrated Pest Management. Conceptually, the model represents a "bottom-up ethological" approach and emulates behavior of the "primary IPM actors"-large cohorts of individu...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00363
更新日期:2016-08-23 00:00:00
abstract::Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise ...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2016.00547
更新日期:2016-11-17 00:00:00
abstract::Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called "β-adrenergic desensitization"). Adrenergic responsiven...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2013.00396
更新日期:2014-01-09 00:00:00
abstract::The physiological mechanisms related to cardio-vascular (CV), cardio-pulmonary (CP), and vasculo-pulmonary (VP) regulation may be probed through multivariate time series analysis tools. This study applied an information domain approach for the evaluation of non-linear causality to the beat-to-beat variability series o...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2011.00080
更新日期:2011-11-07 00:00:00
abstract::In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not th...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.613786
更新日期:2020-12-17 00:00:00
abstract::There is compelling evidence that the "what it feels like" subjective experience of sensory stimuli arises in the cerebral cortex in both humans as well as mammalian experimental animal models. Humans are alone in their ability to verbally communicate their experience of the external environment. In other species, sen...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01027
更新日期:2018-08-02 00:00:00
abstract::This study aimed to investigate the influence of different exercise training modalities [(i) a concurrent training based on physical activity recommendation from the World Health Organization group (PAR group), (ii) a high intensity interval training group (HIIT group), and (iii) a high intensity interval training add...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00451
更新日期:2019-04-24 00:00:00
abstract::Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high vs. low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs) on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric overload with con...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.01074
更新日期:2017-12-19 00:00:00
abstract::We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS) patients into subgroups. To date, we have shown that stratifying based on the presence or absence of comorbid psychiatric diagnosis leads to a grou...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2013.00109
更新日期:2013-05-20 00:00:00
abstract::Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipo-cytokines and metabolic intermediates. These functions are m...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2020.00347
更新日期:2020-04-17 00:00:00
abstract::The sense of taste is responsible for the detection and ingestion of food to cover energetic requirements in health and disease. The change in taste perception might lead to malnutrition that is usually one of the frequent causes of morbidity and mortality in patients with cancer. In this review, we summarize the mech...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2017.00134
更新日期:2017-03-08 00:00:00
abstract:Background:The underlying mechanisms by which diabetes and dyslipidemia contribute to diabetic nephropathy (DN) are not fully understood. In this study, we aimed to investigate the role of high glucose (HG) on intracellular cholesterol accumulation in glomerular endothelial cells (GEnCs) and its potential mechanism. M...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.552483
更新日期:2020-10-19 00:00:00
abstract::The mitochondrial oxidative stress theory of aging posits that membrane susceptibility to peroxidation and the organization of the electron transport system (ETS) linked with reactive oxygen species (ROS) generation are two main drivers of lifespan. While a clear correlation has been established from species comparati...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00946
更新日期:2019-07-26 00:00:00
abstract::Activation of autonomic neural pathways by chronic hypertensive stimuli plays a significant role in pathogenesis of hypertension. Here, we proposed that even a single acute hypertensive stimulus will activate neural and immune pathways that may be important in initiation of memory imprinting seen in chronic hypertensi...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00592
更新日期:2017-08-31 00:00:00
abstract::Secondary shifts develop in post-translational phosphorylation of sarcomeric proteins in multiple animal models of inherited cardiomyopathy. These signaling alterations together with the primary mutation are predicted to contribute to the overall cardiac phenotype. As a result, identification and integration of post-t...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00407
更新日期:2016-09-14 00:00:00
abstract::Muscle tone represents one of the important concepts for characterizing changes in the state of the developing nervous system. It can be manifested in the level of activity of flexors and extensors and in muscle reactions to its passive stretching (StR) or shortening (ShR). Here we investigated such reactions in a coh...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01158
更新日期:2019-09-13 00:00:00
abstract::Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors-OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pl...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2013.00303
更新日期:2013-10-28 00:00:00
abstract::To excrete body nitrogen waste and regulate electrolyte and fluid balance, the kidney has developed into an energy factory with only second to the heart in mitochondrial content in the body to meet the high-energy demand and regulate homeostasis. Energy supply from the renal mitochondria majorly depends on lipid metab...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2020.01050
更新日期:2020-09-03 00:00:00
abstract::Within the vasculature Kv7 channels are key regulators of basal tone and contribute to a variety of receptor mediated vasorelaxants. The Kv7.4 isoform, abundant within the vasculature, is key to these processes and was recently shown to have an obligatory requirement of G-protein βγ subunits for its voltage dependent ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01573
更新日期:2020-01-14 00:00:00
abstract::The purpose of this study was to compare the effects of two similar high-intensity intermittent exercises (HIIE) but different volume 1.25 km (HIIE1.25) and 2.5 km (HIIE2.5) on inflammatory and BDNF responses. Ten physically active male subjects (age 25.22 ± 1.74 years, body mass 78.98 ± 7.31 kg, height 1.78 ± 0.06 m,...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00509
更新日期:2016-11-04 00:00:00
abstract::Introduction: Heart Rate Variability (HRV) and Pulse Rate Variability (PRV), are non-invasive techniques for monitoring changes in the cardiac cycle. Both techniques have been used for assessing the autonomic activity. Although highly correlated in healthy subjects, differences in HRV and PRV have been observed under ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00779
更新日期:2020-07-23 00:00:00
abstract::Background: A range of computational methods that rely on the analysis of genome-wide expression datasets have been developed and successfully used for drug repositioning. The success of these methods is based on the hypothesis that introducing a factor (in this case, a drug molecule) that could reverse the disease ge...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00753
更新日期:2017-09-28 00:00:00
abstract::This study aimed to evaluate the effect of the stretch-shortening cycle (SSC) on different portions of the force-velocity (F-V) relationship in older adults with and without chronic obstructive pulmonary disease (COPD), and to assess its association with physical function. The participants were 26 older adults with CO...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00316
更新日期:2019-03-26 00:00:00