Regulation of cardiac hypertrophy and remodeling through the dual-specificity MAPK phosphatases (DUSPs)

Liu, Ruijie; Molkentin, Jeffery D.

doi:10.1016/j.yjmcc.2016.08.018

Cited by 93 publications

(69 citation statements)

References 93 publications

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“…MAPKs are central signaling intermediates that coordinate diverse physiological and pathological events such as those occurring in cancer, inflammation, diabetes, memory, and cardiac remodeling (Liu and Molkentin, ). MAPK is activated by membrane receptors, or other ill‐defined stress‐sensing effectors, which subsequently activate three major pathways including the p38 MAPK, JNK, and ERK pathways.…”

Section: Discussionmentioning

confidence: 99%

Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

Luo

et al. 2019

Cell Biology International

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B-cell lymphoma 6 (Bcl6) functions as a sequence-specific transcriptional repressor and negative regulator of many signaling proteins. The effects of Bcl6 on cardiomyocyte injury are not clear. This study was designed to determine whether Bcl6 affects hypoxia-induced cardiomyocyte injury and, if so, to identify the underlying mechanism. To meet this aim, cardiomyocytes were exposed to hypoxia and Bcl6 siRNA was used to silence Bcl6 in cardiomyocytes. Bcl6 knockdown under physiological conditions caused increased oxidative stress, apoptosis, and expression of pro-inflammatory cytokines. Increased inflammatory response, oxidative stress, and apoptosis were observed after cells were exposed to hypoxia for 24 h. Bcl6 knockdown aggravated cardiomyocyte injury when exposed to hypoxia. Bcl6 knockdown increased P38 activation without affecting JNK and ERK phosphorylation levels. Treatment with a P38 inhibitor reversed the Bcl6 silencing-induced deteriorating phenotype, as evidenced by reduced inflammatory response, improved oxidative stress response, and increased cell viability. The results indicate that Bcl6 knockdown causes cardiomyocyte injury at baseline conditions and aggravates cardiomyocyte hypoxia injury via activating the P38 pathway.

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Section: Discussionmentioning

confidence: 99%

Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

Luo

et al. 2019

Cell Biology International

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“…Recently, numerous studies have shown that several intracellular signaling pathways might affect the progression of cardiac hypertrophy [18,19]. Notably, it has recently been shown that the hyperactivation of MAPK signaling plays a crucial role in the development of cardiac hypertrophy [20]. JNK is a member of the MAPK pathway and its altered expression is associated with cardiac hypertrophy [21].…”

Section: Discussionmentioning

confidence: 99%

“…Ca 2+ plays a key regulatory role in the metabolic activity and systolic function of cardiomyocytes [12]. Therefore, we also 20 measured the intracellular Ca 2+ concentration with Fluo-3/AM. In this regard, laser confocal microscopy showed that in PE-treated cardiomyocytes, the intracellular Ca 2+ concentration was increased compared to that in controls and that HAT or JNK inhibition could reduce the PE-induced increase in intracellular Ca 2+ .…”

Section: Discussionmentioning

confidence: 99%

Anacardic acid protects against phenylephrine-induced mouse cardiac hypertrophy through JNK signaling-dependent regulation of histone acetylation

Peng

Chang

Luo

et al. 2020

Preprint

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Short title:Anacardic acid protects cardiac hypertrophy through JNK signaling-dependent regulation of histone acetylation Abstract Cardiac hypertrophy is a complex process induced by the activation of multiple signaling pathways. We previously reported that anacardic acid (AA), a histone acetylase (HAT) inhibitor, attenuates phenylephrine (PE)-induced cardiac hypertrophy by downregulating histone H3 acetylation at lysine 9 (H3K9ac). Unfortunately, the upstream signaling events remained unknown. The mitogen-activated protein kinase (MAPK) pathway is an important regulator of cardiac hypertrophy. In this study, we explored the role of JNK/MAPK signaling in cardiac hypertrophy. A mouse model of cardiomyocyte hypertrophy was successfully established in vitro using PE. This study showed that p-JNK directly interacts with HATs (P300 and P300/CBP-associated factor, PCAF) and alters H3K9ac. In addition, both the JNK inhibitor SP600125 and the HAT inhibitor AA attenuated p-JNK overexpression and H3K9 hyperacetylation by inhibiting P300 and PCAF during PE-induced cardiomyocyte hypertrophy.Moreover, we demonstrated that both SP600125 and AA attenuate the overexpression of cardiac hypertrophy-related genes (MEF2A, ANP, BNP, and β-MHC), preventing cardiomyocyte hypertrophy and dysfunction. These results revealed a novel mechanism through which AA might protect mice from PE-induced cardiac hypertrophy. In particular, AA inhibits the effects of JNK signaling on HAT-mediated histone acetylation, and could therefore be used to prevent and treat hypertrophic cardiomyopathy.

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“…TNF‐α, a multifunctional cytokine, has been reported to activate inflammation via activating mitogen‐activated protein kinases (MAPKs) and the nuclear factor ( NF )‐ κB . MAPKs belong to a large family of serine/threonine‐specific kinases including c‐Jun N‐terminal kinase (JNK), ERK and P38 that are demonstrated to be associated with myocardial dysfunction, hypertrophy, fibrosis, and heart failure . The activation of the MAPK signal pathways is also involved in the pathogenesis of diabetic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Deep sea minerals ameliorate diabetic‐induced inflammation via inhibition of TNFα signaling pathways

Day

et al. 2019

Environmental Toxicology

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It has been well‐documented that the consumption of deep sea water (DSW) has beneficial effects on myocardial hypertrophy and cardiac apoptosis induced by hypercholesterolemia. However, the molecular mechanisms for the anti‐inflammatory effects of DSW on diabetic cardiomyopathy are still largely unclear. The main purpose of this present study was to test the hypothesis that DSW exerts anti‐inflammatory effects through the suppression of the TNF‐α‐mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65 mg/kg was used to establish a diabetes rat model. DSW mineral extracts that diluted in desalinated water were prepared in three different dosages and administered to the rats through gavages for 4 weeks. These dosages are DSW‐1X (equivalent to 37 mg Mg2+/kg/day), 2X (equivalent to 74 mg Mg2+/kg/day) and 3X (equivalent to 111 mg Mg2+ mg/kg/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF‐α was markedly higher in the STZ‐induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF‐α‐modulated downstream signaling molecules and P38 mitogen‐activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ‐induced diabetes. These higher phosphorylation levels subsequently upregulated NF‐κB‐modulated inflammatory mediators, such as cyclooxygenase (COX)‐II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO4, the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes‐related cardiovascular diseases.

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Regulation of cardiac hypertrophy and remodeling through the dual-specificity MAPK phosphatases (DUSPs)

Cited by 93 publications

References 93 publications

Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

Anacardic acid protects against phenylephrine-induced mouse cardiac hypertrophy through JNK signaling-dependent regulation of histone acetylation

Deep sea minerals ameliorate diabetic‐induced inflammation via inhibition of TNFα signaling pathways

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