Expression of bcl-2 Protein, an Inhibitor of Apoptosis, and Bax, an Accelerator of Apoptosis, in Ventricular Myocytes of Human Hearts With Myocardial Infarction

Misao, Jun; Hayakawa, Yukihiro; Ohno, Michiya; Kato, Satoshi; Fujiwara, Takako; Fujiwara, Hisayoshi

doi:10.1161/01.cir.94.7.1506

Cited by 338 publications

(232 citation statements)

References 24 publications

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“…SDF-1 increases Bcl-2/Bax ratio through the SDF-1/CXCR4 axis The Bcl-2 family proteins, including the pro-survival Bcl-2 and pro-apoptotic Bax, are key regulators of apoptosis (Misao et al, 1996;Li et al, 2007). To determine whether SDF-1 pretreatment modify the expression of Bcl-2 and Bax, MSCs were pretreated with SDF-1 for 1 h and then exposed to H 2 O 2 followed by re-oxygenation for 16 h. Western blotting showed that Bcl-2 level was increased in SDF-1 pretreated cells, but was significantly lower in AMD3100-treated cells (Fig.…”

Section: Sdf-1 Activates the Akt And Erk Pathways Through The Sdf-1/cmentioning

confidence: 99%

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

et al. 2011

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Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H 2 O 2 for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4. We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.

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Section: Sdf-1 Activates the Akt And Erk Pathways Through The Sdf-1/cmentioning

confidence: 99%

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

et al. 2011

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“…Bcl-2 inhibits cell death by blocking cytochrome C release from the mitochondria [67], that otherwise leads to caspase activation and cell death. Bcl-2 is up-regulated in surviving ventricular myocytes in the context of MI [68], and transgenic over-expression of Bcl-2 in the engrafted cells limits myocardial infarct size after ischemia/reperfusion [69]. Li and colleagues have demonstrated the pro-survival effects of transduced Bcl-2 in two cell types: smooth muscle cells [69] and mesenchymal stem cells [70].…”

Section: Strategies To Increase Cell Survivalmentioning

confidence: 99%

Systems approaches to preventing transplanted cell death in cardiac repair

Robey

Saiget

Reinecke

et al. 2008

Journal of Molecular and Cellular Cardiology

366

294

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Stem cell transplantation may repair the injured heart, but tissue regeneration is limited by death of transplanted cells. Most cell death occurs in the first few days post-transplantation, likely from a combination of ischemia, anoikis and inflammation. Interventions known to enhance transplanted cell survival include heat shock, over-expressing anti-apoptotic proteins, free radical scavengers, anti-inflammatory therapy and co-delivery of extracellular matrix molecules. Combinatorial use of such interventions markedly enhances graft cell survival, but death still remains a significant problem. We review these challenges to cardiac cell transplantation and present an approach to systematically address them.Most anti-death studies use histology to assess engraftment, which is time-and labor-intensive. To increase throughput, we developed two biochemical approaches to follow graft viability in the mouse heart. The first relies on LacZ enyzmatic activity to track genetically modified cells, and the second quantifies human genomic DNA content using repetitive Alu sequences. Both show linear relationships between input cell number and biochemical signal, but require correction for the time lag between cell death and loss of signal. Once optimized, they permit detection of as few as 1 graft cell in 40,000 host cells. Pro-survival effects measured biochemically at three days predict long-term histological engraftment benefits. These methods permitted identification of carbamylated erythropoietin (CEPO) as a pro-survival factor for human embryonic stem cell-derived cardiomyocyte grafts. CEPO's effects were additive to heat shock, implying independent survival pathways. This system should permit combinatorial approaches to enhance graft viability in a fraction of the time required for conventional histology.

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“…Bifunctional apoptosis regulator (BAR) is an endoplasmic reticulum protein that inhibits cardiomyocyte apoptosis through interacting with the intrinsic apoptosis pathway (Chua et al, 2009). Bcl-2 protects cardiomyocyte from apoptosis (Misao et al, 1996;Imahashi et al, 2004). And cardiac specific Bcl-2 transgenic mice exhibit reduced infarct size and cardiomyocyte apoptosis (Brocheriou et al, 2000;Chen et al, 2001).…”

Section: Mitochondria Mediate Apoptosis In Heartmentioning

confidence: 99%

Mitochondrial network in the heart

Zhou

Gao

et al. 2012

Protein Cell

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Mitochondria are subcellular organelles that provide energy for the cell. They form a dynamic tubular network and play an important role in maintaining the cell function and integrity. Heart is a powerful organ that supplies the motivation for circulation, thereby requiring large amounts of energy. Thus, the healthiness of cardiomyocytes and mitochondria is necessary for the normal cardiac function. Mitochondria not only lie in the center of the cell apoptotic pathway, but also are the major source of reactive oxygen species (ROS) generation. Mitochondrial morphological change includes fission and fusion that are regulated by a large number of proteins. In this review we discuss the regulators of mitochondrial fission/fusion and their association with cell apoptosis, autophagy and ROS production in the heart.

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Expression of bcl-2 Protein, an Inhibitor of Apoptosis, and Bax, an Accelerator of Apoptosis, in Ventricular Myocytes of Human Hearts With Myocardial Infarction

Cited by 338 publications

References 24 publications

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

Systems approaches to preventing transplanted cell death in cardiac repair

Mitochondrial network in the heart

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