CCN1 enables Fas ligand-induced apoptosis in cardiomyoblast H9c2 cells by disrupting caspase inhibitor XIAP

Su, Bor Chyuan; Mo, Fan

doi:10.1016/j.cellsig.2014.02.019

Cited by 20 publications

(31 citation statements)

References 42 publications

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“…CCN1 promotes cardiomyocyte apoptosis through potentiating the death effect of FasL [12, 13]. We examined the induction of FasL after DOX treatment by immunohistochemical staining with anti-FasL antibody.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the pivotal role of FasL and its receptor Fas in cardiac injury, the activation of Fas signaling alone is not sufficient to induce apoptosis in mouse hearts or in cultured cardiomyocytes [10, 11]. CCN1, a matricellular protein, sensitizes cardiomyocytes to FasL-induced apoptosis both in mice and in cultured cells [12, 13]. CCN1 promotes various cell activities and regulates cell survival and death through interaction with distinct integrin receptors in a cell type- and context-dependent manner [14].…”

Section: Introductionmentioning

confidence: 99%

“…CCN1 is also induced in mice with work-overload-induced cardiac injury, and sensitizes FasL-mediated cardiomyocyte apoptosis by engaging its cell-surface receptor integrin α 6 β 1 [12]. CCN1/α 6 β 1 signaling triggers the accumulation of cellular ROS, activation of p38 mitogen-activated protein kinase (MAPK), and translocation of mitochondrial Smac and HtrA2 to cytosol, thereby counteracting the anti-apoptotic activity of XIAP and facilitating FasL-induced apoptosis in cardiomyocytes [13]. …”

Section: Introductionmentioning

confidence: 99%

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Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

Hsu

2016

Oncotarget

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Doxorubicin (DOX) is an effective chemotherapeutic agent however its clinical use is limited by its cumulative cardiotoxicity. Matricellular protein CCN1 mediates work-overload-induced cardiac injury. We aimed to assess the role of CCN1 in DOX-associated cardiomyopathy. Here we discovered CCN1 expression in the myocardium 1 day after DOX treatment (15 mg/kg; i.p.) in mice. Whereas CCN1 synergizes with Fas ligand (FasL) to induce cardiomyocyte apoptosis, we found that FasL was also induced by DOX in the heart. To assess the function of CCN1 in vivo, knockin mice (Ccn1dm/dm) expressing an β6β1-binding defective CCN1 mutant were treated with a single dose of DOX (15 mg/kg; i.p.). Compared with wild-type mice, Ccn1dm/dm mice were resistant to DOX-induced cardiac injury and dysfunction 14 days after injection. Using rat cardiomyoblast H9c2 cells, we demonstrated that DOX induced reactive oxygen species accumulation to upregulate CCN1 and FasL expression. CCN1 mediated DOX cardiotoxicity by engaging integrin β6β1 to promote p38 mitogen-activated protein kinase activation and the release of mitochondrial Smac and HtrA2 to cytosol, thereby counteracting the inhibition of XIAP and facilitating apoptosis. In summary, CCN1 critically mediates DOX-induced cardiotoxicity. Disrupting CCN1/β6β1 engagement abolishes DOX-associated cardiomyopathy in mice.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

Hsu

2016

Oncotarget

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“…Eventually, umprocessed Smac proteins containing 184 amino acid residues are generated, with the apoptotic activity acquired simultaneously. [3,9] The mechanism of Smac in the cell apoptosis is as follows: [10,11] (1) Smac can directly interact with Caspase-9 to enhance cascade reactions of Caspases, increase the sensitivity of tumor cells to the apoptosis stimulation and promote cell apoptosis. (2) Smac can also enhance the activity of Caspase-3 by promoting the proteolysis of pro-Caspase-3, while the activated Caspase-3 in turn activates Caspase-9 zymogens.…”

Section: Smac and Endometriosismentioning

confidence: 99%

Expression of Bcl-2, Smac and their correlation in endometriosis

Zhu

Shen

2017

DCC

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Objective: To explore the expression of anti-apoptotic gene Bcl-2 and second mitochondria-derived activator of caspases (Smac) in endometriosis, the relationship of Bcl-2 and Smac with clinical staging and menstrual cycle, as well as correlation analysis. Methods: Thirty samples of endometrial tissues taken from endometriosis patients were chosen as the study group (endometriosis group), including 16 cases in the proliferative phase and 14 cases in the secretory phase. Thirty samples of normal endometrial tissues were chosen as the control group. Immunohistochemical method (SP) was used to determine the expression of Bcl-2 and Smac proteins in each group. Statistical analysis was carried out with SPSS 16.0 statistical package. The comparison of measurement data between two groups was made by use of chi-square (χ 2 ) test, and the correlation test of two indexes was performed by use of Spearman's correlation analysis. The difference in statistical data was of statistical significance (p < .05). Results: The expression of Bcl-2 in eutopic and ectopic endometrial tissues in the endometriosis group was significantly higher than that in normal endometrial tissues in the control group, and the difference was statistically significant (p < .05). The difference of Bcl-2 expression in all phases of both eutopic tissues in the endometriosis group and normal endometrial tissues was statistically significant (p < .05), the positive expression in the secretory phase was obviously lower than that in the proliferative phase. The expression intensity of Smac in eutopic and ectopic endometrial tissues in the endometriosis group was lower than that in normal endometrial tissues in the control group, and the difference was of statistical significance (p < .05). The expression intensity of Smac in ectopic endometrial tissues was lower than that in eutopic endometrial tissues, and the difference was of statistical significance (p < .05); the expression intensity of Smac in the secretory phase was higher than that in the proliferative phase in normal endometrial tissues (p < .05). The expression of Bcl-2 and Smac was not related to clinical staging of endometriosis (p > .05). The expression of Bcl-2 was negatively correlated to the expression of Smac (p < .05). Conclusions: The high expression of Bcl-2 and the low expression of Smac enhance the abilities of hyperplasia and antiapoptosis of ectopic endometrial cells, which leads to the occurrence and development of endometriosis.

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“…Once activated by caspase, it triggers an irreversible cascade reaction 16 .The inhibitor of apoptosis proteins(IAPs) family may regulate the activation of caspase, including c-IAPl, c-IAP2, XIAP and Survivin. XIAP, directly associated with Caspase-3, caspase-7 and caspase-9, is the strongest caspase inhibitor 17 . Saito et al 18 believe that activation of the XIAP pathway occurs prior to the activation of caspase cascade, and the interaction between XIAP and Smac and caspase is critical for neuronal cell death after cerebral ischemia.…”

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confidence: 99%

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

Wang

et al. 2018

Acta Cir. Bras.

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Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemiareperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B [intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model], and group C [intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model]. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

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CCN1 enables Fas ligand-induced apoptosis in cardiomyoblast H9c2 cells by disrupting caspase inhibitor XIAP

Cited by 20 publications

References 42 publications

Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

Matricellular protein CCN1 mediates doxorubicin-induced cardiomyopathy in mice

Expression of Bcl-2, Smac and their correlation in endometriosis

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

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