Partial Inactivation of Cardiac 14-3-3 Protein &lt;i&gt;in vivo&lt;/i&gt; Elicits Endoplasmic Reticulum Stress (ERS) and Activates ERS-initiated Apoptosis in ERS-induced Mice

Sari, Flori R.; Watanabe, Kenichi; Widyantoro, Bambang; Thandavarayan, Rajarajan Amirthalingam; Harima, Meilei; Zhang, Shaosong; Muslin, Anthony J.; Kodama, Makoto; Aizawa, Yoshifusa

doi:10.1159/000320548

Cited by 15 publications

(8 citation statements)

References 39 publications

(66 reference statements)

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“…In this study, we performed ascending AB surgery since this technique provides a more direct and rapid source of pressure overload on the LV together with a significant degree of hypertrophy after 48 hours [15,16]. We have shown that seven days pressure overload induced by AB surgery resulted in similar increases in the HW/BW ratio, cardiomyocyte diameter, and the expression levels of cardiac ANP and galectin-3 in the WT and DN p38 mice.…”

Section: Discussionmentioning

confidence: 97%

“…To induce pressure overload in the mice, we performed ascending AB surgery, since this technique provides a more direct and rapid source of pressure overload on the left ventricle (LV) with a significant degree of hypertrophy after 48 hours [15,16]. Ten-to twelve-week-old male WT (WT AB; n = 6) and DN p38 MAPK mice (DN p38 AB; n = 7) were anesthetized intraperitoneally with Nembutal 50 mg/kg body weight.…”

Section: Ascending Aortic Banding (Ab) Surgerymentioning

confidence: 99%

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Attenuation of CHOP-mediated Myocardial Apoptosis in Pressure-overloaded Dominant Negative p38α Mitogen-activated Protein Kinase Mice

Sari

Widyantoro

Thandavarayan

et al. 2011

Cell Physiol Biochem

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Background/Aims: Pressure overload stimulation is known to elicit disturbances in the endoplasmic reticulum (ER), which leads to ER stress (ERS). p38 mitogen-activated protein kinase (MAPK) plays an important role in mediating apoptotic processes, however, the roles of this kinase in activating ERS-initiated apoptosis in pressure-overloaded hearts are largely unknown. Methods: We clarified the role of p38α MAPK in ERS-associated apoptosis by subjecting transgenic mice displaying cardiac specific dominant negative (DN) mutant p38α MAPK over-expression to seven day pressure overload. Results: Seven days pressure overload resulted in the same extent of cardiac hypertrophy and ERS in the wild-type (WT) and DN p38α mice compared with the sham mice. It also activated inositol-requiring enzyme (Ire)-1α and its downstream molecule, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2 in the WT and DN p38α mice compared with the sham mice. Interestingly, increased myocardial apoptosis and the up-regulation of CCAAT/enhancer binding protein homology protein (CHOP) expression compared with those in the sham mice were found in the aortic-banded WT mice, but not in the DN p38α mice. Conclusion: Partial inhibition of p38α protein blocked the activation of CHOP-mediated apoptotic processes during pressure overload by partially inhibiting signaling from the Ire-1α/TRAF2 to its down-stream molecule, CHOP.

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Section: Discussionmentioning

confidence: 97%

Section: Ascending Aortic Banding (Ab) Surgerymentioning

confidence: 99%

Attenuation of CHOP-mediated Myocardial Apoptosis in Pressure-overloaded Dominant Negative p38α Mitogen-activated Protein Kinase Mice

Sari

Widyantoro

Thandavarayan

et al. 2011

Cell Physiol Biochem

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“…Phosphorylations at S43, S233, and S259 sterically inhibit Raf-1 binding to GTP-Ras and promote, instead, binding to the adapter/chaperone protein 14-3-3 (named for the separation fraction where it was discovered). Various 14-3-3 isoforms often hold proinflammatory client proteins like Raf1 inactive in the cytoplasm as shown in FIGURE 3 (1537,2103,2125). There is a suggestion that upregulation of 14-3-3 proteins may be protective in atherosclerosis, although assignment of specific roles for the different isoforms is difficult (218,1052).…”

Section: Activation Of Raf1 a Prototypical Map3k And Other Activatomentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

390

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…Cardiac specific expression of a dominate negative-14–3–3 protein in mice increased apoptotic cell death under stress such as cardiac hypertrophy, diabetic cardiomyopathy, and heart failure, suggesting that 14–3–3 proteins are essential for cardioprotection during stress to the heart [40]. …”

Section: Resultsmentioning

confidence: 99%

Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation

Liu

Jain

et al. 2015

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Thioredoxin 1 (Trx1) is a antioxidant protein that regulates protein disulfide bond reduction, transnitrosylation, denitrosylation and other redox post-translational modifications. In order to better understand how Trx1 modulates downstream protective cellular signaling events following cardiac ischemia, we conducted an expression proteomics study of left ventricles (LVs) after thoracic aortic constriction stress treatment of transgenic mice with cardiac-specific over-expression of Trx1, an animal model that has been proven to withstand more stress than its non-transgenic littermates. Although previous redox post-translational modifications proteomics studies found that several cellular protein networks are regulated by Trx1-mediated disulfide reduction and transnitrosylation, we found that Trx1 regulates the expression of a limited number of proteins. Among the proteins found to be upregulated in this study was SET and MYND domain-containing protein 1 (SMYD1), a lysine methyltransferase highly expressed in cardiac and other muscle tissues and an important regulator of cardiac development. The observation of SMYD1 induction by Trx1 following thoracic aortic constriction stress is consistent with the retrograde fetal gene cardiac protection hypothesis. The results presented here suggest for the first time that, in addition to being a master redox regulator of protein disulfide bonds and nitrosation, Trx1 may also modulate lysine methylation, a non-redox post-translational modification, via the regulation of SMYD1 expression. Such crosstalk between redox signaling and a non-redox PTM regulation may provide novel insights into the functions of Trx1 that are independent from its immediate function as a protein reductase.

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Partial Inactivation of Cardiac 14-3-3 Protein <i>in vivo</i> Elicits Endoplasmic Reticulum Stress (ERS) and Activates ERS-initiated Apoptosis in ERS-induced Mice

Cited by 15 publications

References 39 publications

Attenuation of CHOP-mediated Myocardial Apoptosis in Pressure-overloaded Dominant Negative p38α Mitogen-activated Protein Kinase Mice

Attenuation of CHOP-mediated Myocardial Apoptosis in Pressure-overloaded Dominant Negative p38α Mitogen-activated Protein Kinase Mice

Molecular Biology of Atherosclerosis

Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation

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