Scaffold Proteins Regulating Extracellular Regulated Kinase Function in Cardiac Hypertrophy and Disease

Liang, Yan; Sheikh, Farah

doi:10.3389/fphar.2016.00037

Cited by 18 publications

(11 citation statements)

References 69 publications

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“…However, its role in cardiac hypertrophy has yet to be investigated. Instead, other ERK-associated scaffolding proteins have been shown to play a central role in the maintenance of cardiomyocyte physiology and the induction of adaptive hypertrophy [40]. We have already mentioned β-arrestin as an important scaffold for ERK activation in response to GPCRs (see above).…”

Section: The Role Of Erk In Adaptive Cardiac Hypertrophymentioning

confidence: 99%

“…These proteins are myofilament-associated proteins highly induced during the hypertrophic process in mice and humans and are components of the sarcomere-associated biomechanical sensors. Loss of function studies highlighted that both proteins, FHL1 and ANKRD1, have detrimental roles in Gαq and phenylephrine-induced cardiac hypertrophy [40]. Fhl1 −/− hearts displayed a blunted response to pathological hypertrophy [48].…”

Section: The Role Of Erk In Adaptive Cardiac Hypertrophymentioning

confidence: 99%

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ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy

Gallo

Vitacolonna

Bonzano

et al. 2019

IJMS

190

138

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Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic hypertrophy and may lead to heart failure. In this review, we analyze the recent literature regarding the role of ERK (extracellular signal-regulated kinase) activity in cardiac hypertrophy. ERK signaling produces beneficial effects during the early phase of chronic pressure overload in response to G protein-coupled receptors (GPCRs) and integrin stimulation. These functions comprise (i) adaptive concentric hypertrophy and (ii) cell death prevention. On the other hand, ERK participates in maladaptive hypertrophy during hypertension and chemotherapy-mediated cardiac side effects. Specific ERK-associated scaffold proteins are implicated in either cardioprotective or detrimental hypertrophic functions. Interestingly, ERK phosphorylated at threonine 188 and activated ERK5 (the big MAPK 1) are associated with pathological forms of hypertrophy. Finally, we examine the connection between ERK activation and hypertrophy in (i) transgenic mice overexpressing constitutively activated RTKs (receptor tyrosine kinases), (ii) animal models with mutated sarcomeric proteins characteristic of inherited hypertrophic cardiomyopathies (HCMs), and (iii) mice reproducing syndromic genetic RASopathies. Overall, the scientific literature suggests that during cardiac hypertrophy, ERK could be a “good” player to be stimulated or a “bad” actor to be mitigated, depending on the pathophysiological context.

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Section: The Role Of Erk In Adaptive Cardiac Hypertrophymentioning

confidence: 99%

Section: The Role Of Erk In Adaptive Cardiac Hypertrophymentioning

confidence: 99%

ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy

Gallo

Vitacolonna

Bonzano

et al. 2019

IJMS

190

138

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“… 12 , 13 CBD administered directly into key brain regions reduces anxiety-like behavior in rodents. 14–16 CBD may also reduce anxiety and alleviate other neurological disorders by enhancing anandamide through fatty acid amide hydrolase inhibition 17 , 18 or by altering serotonergic (5-HT) neurotransmission, including actions as an indirect 5-HT1A agonist. 1 , 18–21 …”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Does Not Dampen Responses to Emotional Stimuli in Healthy Adults

Wit

2017

Cannabis and Cannabinoid Research

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Introduction: Cannabidiol (CBD) is a nonpsychoactive constituent of whole plant cannabis that has been reported to reduce anxiety-like behaviors in both pre-clinical and human laboratory studies. Yet, no controlled clinical studies have demonstrated its ability to reduce negative mood or dampen responses to negative emotional stimuli in humans. The objective of this study was to investigate the effects of CBD on responses to negative emotional stimuli, as a model for its potential anxiety-reducing effects.Materials and Methods: The study used a double-blind, placebo (PLB)-controlled, within-subjects design in which 38 healthy, drug-free participants consumed oral CBD (300, 600, and 900 mg) or PLB before completing several behavioral tasks selected to assess reactivity to negative stimuli. Dependent measures included emotional arousal to negative and positive visual stimuli, perceptual sensitivity to emotional facial expressions, attentional bias toward emotional facial expressions, and feelings of social rejection. In addition, subjective drug effects and physiological data were also gathered during each experimental session to assess drug effects.Discussion: CBD did not dampen responses to negative emotional stimuli and did not affect feelings of social rejection. The high dose of CBD (900 mg) marginally reduced attentional bias toward happy and sad facial expressions, and produced a slight increase in late-session heart rate. CBD did not produce detectable subjective effects or alterations in mood or anxiety.Conclusion: These findings indicate that CBD has minimal behavioral and subjective effects in healthy volunteers, even when they are presented with emotional stimuli. Further research into the behavioral and neural mechanisms of CBD and other phytocannabinoids is needed to ascertain the clinical function of this drug.

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“…Finally, with regard to the enrichment results for hypertrophy, four out of the top nine functions related to the extracellular space were enriched in the sLDA-inferred markers. The authors of some previous studies have reported the relatedness between hypertrophy and the extracellular region of the heart, chondrocytes, and astrocytes [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. In particular, Yang et al [ 29 ] concluded that SCUBE3, which is an extracellular protein, may account for the accelerated onset and progression of cardiac hypertrophy.…”

Section: Resultsmentioning

confidence: 99%

Inferring Genes and Biological Functions That Are Sensitive to the Severity of Toxicity Symptoms

Kim¹,

Shin²

2017

IJMS

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The effective development of new drugs relies on the identification of genes that are related to the symptoms of toxicity. Although many researchers have inferred toxicity markers, most have focused on discovering toxicity occurrence markers rather than toxicity severity markers. In this study, we aimed to identify gene markers that are relevant to both the occurrence and severity of toxicity symptoms. To identify gene markers for each of four targeted liver toxicity symptoms, we used microarray expression profiles and pathology data from 14,143 in vivo rat samples. The gene markers were found using sparse linear discriminant analysis (sLDA) in which symptom severity is used as a class label. To evaluate the inferred gene markers, we constructed regression models that predicted the severity of toxicity symptoms from gene expression profiles. Our cross-validated results revealed that our approach was more successful at finding gene markers sensitive to the aggravation of toxicity symptoms than conventional methods. Moreover, these markers were closely involved in some of the biological functions significantly related to toxicity severity in the four targeted symptoms.

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Scaffold Proteins Regulating Extracellular Regulated Kinase Function in Cardiac Hypertrophy and Disease

Cited by 18 publications

References 69 publications

ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy

ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy

Cannabidiol Does Not Dampen Responses to Emotional Stimuli in Healthy Adults

Inferring Genes and Biological Functions That Are Sensitive to the Severity of Toxicity Symptoms

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