Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival

Zhang, Shaosong; Ren, Jie; Zhang, Cindy E.; Treskov, Ilya; Wang, Yibin; Muslin, Anthony J.

doi:10.1161/01.res.0000104084.88317.91

Cited by 43 publications

(36 citation statements)

References 13 publications

(19 reference statements)

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“…Mice expressing a dominant-negative form of 14-3-3η (DN-14-3-3) are unable to compensate for pressure overload resulting in increased myocyte apoptosis and mortality. DN-14-3-3/DNp38β mice, and to a lesser extent DN-14-3-3/DN-p38α mice, show reduced mortality and cardiac myocyte apoptosis in response to pressure overload [35]. Taken together, these data indicate that, although expressed at lower levels than p38α or p38γ, p38β plays a distinct role in the heart.…”

Section: Discussionmentioning

confidence: 72%

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

Dingar

Merlen

Grandy

et al. 2010

Cellular Signalling

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Abstractp38 mitogen-activated protein kinases (MAPKs) are serine/threonine specific protein kinases that respond to cellular stress and regulate a broad range of cellular activities. There are four major isoforms of p38MAPK:α, β, γ, and δ. To date, the prominent isoform in heart has been thought to be p38α. We examined the expression of each p38 isoform at both the mRNA and protein level in murine heart. mRNA for all four p38 isoforms was detected. p38γ and p38δ were expressed at protein levels comparable to p38α and 38β, respectively. In the early phase of pressure-overload hypertrophy (1-7 days after constriction of the transverse aorta), the abundance of p38β, p38γ and p38δ mRNA increased; however, no corresponding changes were detected at the protein level. Confocal immunofluorescence studies revealed p38α and p38γ in both the cytoplasm and nucleus. In the established phase of hypertrophy induced by chronic pressure overload (7-28 days after constriction of the transverse aorta), p38γ immunoreactivity accumulated in the nucleus whereas the distribution of p38α remained unaffected. Hence, both p38α and p38γ are prominent p38 isoforms in heart and p38γ may play a role in mediating the changes in gene expression associated with cardiac remodeling during pressure-overload hypertrophy.

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Section: Discussionmentioning

confidence: 72%

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

Dingar

Merlen

Grandy

et al. 2010

Cellular Signalling

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“…For example, it has been reported that the inhibition of T-cell antigen receptormediated Shc-Grb2 signaling complex or the decrease of Grb2 expression in mice result in a defective TCR-induced p38 MAPK activation [97,100]. The 14-3-3 protein has also been reported to participate in the regulation of p38 MAPK activation [102][103][104] and to form a signaling complex with PI3 K [105,106]. Clearly it will be important to determinate other components of the PI3-K-p38 signaling complex to understand the mechnanism of P-selectinmediated β1 integrin activation.…”

Section: Discussionmentioning

confidence: 99%

P-selectin activates integrin-mediated colon carcinoma cell adhesion to fibronectin

Reyes‐Reyes

George

Roberts

et al. 2006

Experimental Cell Research

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During hematogenous cancer metastasis, tumor cells separate from a primary mass, enter the bloodstream, disperse throughout the body, migrate across vessel walls, and generate distant colonies. The later steps of metastasis superficially resemble leukocyte extravasation, a process initiated by selectin-mediated cell tethering to the blood vessel wall followed by integrin-mediated arrest and transendothelial migration. Some cancer cells express P-selectin ligands and attach to immobilized Pselectin, suggesting that these cells can arrest in blood vessels using sequential selectin-and integrin-mediated adhesion, as do leukocytes. We hypothesize that selectin binding may regulate subsequent integrin-mediated steps in metastasis. Using a model system of cultured Colo 320 human colon adenocarcinoma cells incubated with soluble P-selectin-IgG chimeric protein, we have found that P-selectin can stimulate activation of the α 5 β 1 integrin resulting in a specific increase of adhesion and spreading of these cells on fibronectin substrates. P-selectin binding also induced activation of p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (PI3-K). PI3-K inhibitors blocked P-selectin-mediated integrin activation, cell attachment, and cell spreading. Inhibition of p38 MAPK activation blocked cell spreading, but not cell attachment. P-Selectin binding also resulted in formation of a signaling complex containing PI3-K and p38 MAPK. These results suggest that P-selectin binding to tumor cells can activate α 5 β 1 integrin via PI3-K and p38 MAPK signaling pathways leading to increased cell adhesion. We propose that P-selectin ligands are important tumor cell signaling molecules that modulate integrin-mediated cell adhesion in the metastatic process.

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“…We have shown previously that compound transgenic DNp38␣ and DNp38␤ mice display resistance to myocardial injury after pressure overload (28), demonstrating that the enhanced survival observed in these mice is a consequence of p38 MAPK inhibition that is 14-3-3 mediated. To establish whether inhibition of p38 MAPK can reverse the DN 14-3-3 phenotype after swimming stress, we treated DN 14-3-3 mice with FR-167653 (p38 MAPK inhibitor) in the present study.…”

Section: Translational Physiologymentioning

confidence: 92%

Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK

Watanabe

Ma²,

Hirabayashi³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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It is generally believed that a mechanical signal initiates a cascade of biological events leading to coordinated cardiac remodeling. 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. To evaluate the molecular mechanism underlying swimming stress-induced cardiac remodeling, we examined the role of 14-3-3 protein and MAPK pathway by pharmacological and genetic means using transgenic mice with cardiac-specific expression of dominant-negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38α/β MAPK (DNp38α and DNp38β) mice. p38 MAPK activation was earlier, more marked, and longer in the myocardium of the TG group compared with that of the nontransgenic (NTG) group after swimming stress, whereas JNK activation was detected on day 5 and decreased afterward. In contrast, ERK1/2 was not activated after swimming stress in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were greatly increased in the TG group compared with those in the NTG group. Moreover, we found a significant correlation between p38 MAPK activation and apoptosis in the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic peptide expression. In contrast, DNp38α and DNp38β mice exhibited reduced mortality and increased resistance to cardiac remodeling after 28 days of swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis and improvement in the survival rate in the TG group. These results indicate for the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in left ventricular remodeling associated with swimming stress.

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Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival

Cited by 43 publications

References 13 publications

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

P-selectin activates integrin-mediated colon carcinoma cell adhesion to fibronectin

Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK

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