The chemical chaperone 4-phenylbutyric acid attenuates pressure-overload cardiac hypertrophy by alleviating endoplasmic reticulum stress

Park, Chang Sik; Cha, Hyeseon; Kwon, Eun Young; Sreenivasaiah, Pradeep Kumar; Kim, Do Han

doi:10.1016/j.bbrc.2012.04.048

Cited by 82 publications

(59 citation statements)

References 34 publications

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“…However, the potential role of ERS in pathophysiological hearts remains unclear. Park et al [128] demonstrated that pressure overload caused by transverse aortic constriction (TAC) induced prolonged ERS, which was performed in the upregulation of ERS chaperones GRP78, p-PERK, p-elF2α, CHOP, caspase 12 and p-JNK, and then contributed to cardiac myocyte apoptosis in hypertrophy. Apart from these changes in TAC model, ERS chaperones GRP78, caspase 12 and JNK increased abdominal aortic constriction (AAC) in rats [129] .…”

Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

“…Its physiochemical properties make it possible to stabilize peptide structures and improve luminal folding capacity and traffic of aberrant proteins [171] . Park et al [128] reported that oral administration of PBA to TAC mice reduced the expression of GRP78, p-PERK and p-elF2α. PBA also severely downregulated hypertrophy and fibrosis related genes (TGF-β1, phospho-smad2, and pro-collagen isoforms).…”

Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

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Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

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Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.

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Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

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“…It is well established that increased arterial blood pressure is associated with cardiovascular complications, such as hypertrophy, fibrosis, renal failure, and vascular endothelial dysfunction. Cardiac hypertrophy and fibrosis are well documented in hypertensive animals and patients (72,76). Hypertension-induced cardiac hypertrophy is a progressive event that is associated with myocardial remodeling which is characterized by fibrosis and alterations in cardiomyocyte size and function.…”

Section: Santos Et Almentioning

confidence: 99%

Endoplasmic Reticulum Stress and Nox-Mediated Reactive Oxygen Species Signaling in the Peripheral Vasculature: Potential Role in Hypertension

Santos

Nabeebaccus

Shah

et al. 2014

Antioxidants & Redox Signaling

121

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Significance: Reactive oxygen species (ROS) are produced during normal endoplasmic reticulum (ER) metabolism. There is accumulating evidence showing that under stress conditions such as ER stress, ROS production is increased via enzymes of the NADPH oxidase (Nox) family, especially via the Nox2 and Nox4 isoforms, which are involved in the regulation of blood pressure. Hypertension is a major contributor to cardiovascular and renal disease, and it has a complex pathophysiology involving the heart, kidney, brain, vessels, and immune system. ER stress activates the unfolded protein response (UPR) signaling pathway that has prosurvival and proapoptotic components. Recent Advances: Here, we summarize the evidence regarding the association of Nox enzymes and ER stress, and its potential contribution in the setting of hypertension, including the role of other conditions that can lead to hypertension (e.g., insulin resistance and diabetes). Critical Issues: A better understanding of this association is currently of great interest, as it will provide further insights into the cellular mechanisms that can drive the ER stress-induced adaptive versus maladaptive pathways linked to hypertension and other cardiovascular conditions. More needs to be learnt about the precise signaling regulation of Nox(es) and ER stress in the cardiovascular system. Future Directions: The development of specific approaches that target individual Nox isoforms and the UPR signaling pathway may be important for the achievement of therapeutic efficacy in hypertension. Antioxid. Redox Signal. 20,[121][122][123][124][125][126][127][128][129][130][131][132][133][134]

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“…1 Cardiomyocyte hypertrophy is a complex cellular reprogramming process involving myriads of biomolecular mechanisms, among which endoplasmic reticulum stress (ERS) and reactive oxygen species (ROS) are increasingly regarded as important mechanisms of cardiac hypertrophy. [2][3][4][5][6] ERS, the disruption of ER homeostasis, initiates 3 major signaling pathways to restore ER homeostasis. These signaling pathways, collectively known as unfolded protein response (UPR), comprise protein kinase RNA-like ER kinase (PERK)/ eukaryotic initiation factor 2a(eIF2a)/activating transcriptional factor 4(ATF4), inositol-requiring protein 1a (IRE1a)/Xbp1s and activating transcriptional factor 6 (ATF6) signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Critical role of X-box binding protein 1 in NADPH oxidase 4-triggered cardiac hypertrophy is mediated by receptor interacting protein kinase 1

Chen

Zhao

et al. 2017

Cell Cycle

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NADPH oxidase 4 (NOX4) and the NOX4-related redox signaling are implicated in cardiac hypertrophy. NOX4 is interrelated with endoplasmic reticulum stress (ERS). Spliced X-box binding protein 1 (Xbp1s) is a key mediator of ERS while its role in cardiac hypertrophy is still poorly understood. Recently, receptor interacting protein kinase 1(RIPK1) has been increasingly reported to be associated with ERS. Therefore, we aimed to test the hypothesis that Xbp1s mediates NOX4-triggered cardiac hypertrophy via RIPK1 signaling. In the heart tissue of transverse aortic constriction (TAC) rats and in primary cultured neonatal cardiomyocytes(NCMs) treated with angiotensinII(AngII) or isoproterenol (ISO), NOX4 expression and reactive oxygen species (ROS) generation, and expression of Xbp1s as well as RIPK1-related phosphorylation of P65 subunit of NF-kB were elevated. Gene silencing of NOX4 by specific small interfering RNA (siRNA) significantly blocked the upregulation of NOX4, generation of ROS, splicing of Xbp1 and activation of the RIPK1-related NF-kB signaling, meanwhile attenuated cardiomyocyte hypertrophy. In addition, ROS scavenger (N-acetyl-L-cysteine, NAC) and NOX4 inhibitor GKT137831 reduced ROS generation and alleviated activation of Xbp1 and RIPK1-related NF-kB signaling. Furthermore, splicing of Xbp1 was responsible for the increase in RIPK1 expression in AngII or ISO-treated NCMs. Upregulated RIPK1 in turn activates NF-kB signaling in a kinase activity-independent manner. These findings suggest that Xbp1s plays an important role in NOX4-triggered cardiomyocyte hypertrophy via activating its downstream effector RIPK1, which may prove significant for the development of future therapeutic strategies. KEYWORDS cardiac hypertrophy; endoplasmic reticulum stress; NADPH oxidase 4; receptor interacting protein kinase 1; X-box binding protein 1

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The chemical chaperone 4-phenylbutyric acid attenuates pressure-overload cardiac hypertrophy by alleviating endoplasmic reticulum stress

Cited by 82 publications

References 34 publications

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

Endoplasmic Reticulum Stress and Nox-Mediated Reactive Oxygen Species Signaling in the Peripheral Vasculature: Potential Role in Hypertension

Critical role of X-box binding protein 1 in NADPH oxidase 4-triggered cardiac hypertrophy is mediated by receptor interacting protein kinase 1

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