Increased Cardiomyocyte Apoptosis and Changes in Proapoptotic and Antiapoptotic Genes
            <i>bax</i>
            and
            <i>bcl</i>
            -2 During Left Ventricular Adaptations to Chronic Pressure Overload in the Rat

Condorelli, Gianluigi; Morisco, Carmine; Stassi, Giorgio; Notte, Antonella; Farina, Felicia; Sgaramella, Giuseppe; Rienzo, Assunta De; Roncarati, Roberta; Trimarcö, Bruno; Lembo, Giuseppe

doi:10.1161/01.cir.99.23.3071

Cited by 257 publications

(199 citation statements)

References 19 publications

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“…Ikeda et al (17) reported no change in the expression of either Bax or Bcl2 proteins between the stages of hypertrophy and failure in spontaneously hypertensive rats. Induction of Bax, but not Bcl2, was observed during the transition to left ventricular dysfunction during chronic pressure overload in rats (11). Our study in 9-month-old Tg mice overexpressing myotrophin showed a significant increase in both the pro-apoptotic gene Bax, as well as the anti-apoptotic gene Bcl2, at both RNA and protein levels during transition from hypertrophy to heart failure.…”

Section: Figmentioning

confidence: 43%

Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

Sarkar¹,

Chawla‐Sarkar²,

Young³

et al. 2004

Journal of Biological Chemistry

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Cardiac hypertrophy and ensuing heart failure are among the most common causes of mortality worldwide, yet the triggering mechanisms for progression of hypertrophy to failure are not fully understood. Tissue homeostasis depends on proper relationships between cell proliferation, differentiation, and death and any imbalance between them results in compromised cardiac function. Recently, we developed a transgenic (Tg) mouse model that overexpress myotrophin (a 12-kDa protein that stimulates myocyte growth) in heart resulting in hypertrophy that progresses to heart failure. This provided us an appropriate model to study the disease process at any point from initiation of hypertrophy end-stage heart failure. We studied detailed apoptotic signaling and regenerative pathways and found that the Tg mouse heart undergoes myocyte loss and regeneration, but only at a late stage (during transition to heart failure). Several apoptotic genes were up-regulated in 9-month-old Tg hearts compared with age-matched wild type or 4-week-old Tg hearts. Cardiac cell death during heart failure involved activation of Fas, tumor necrosis factor-␣, and caspases 9, 8, and 3 and poly(ADP-ribose) polymerase cleavage. Tg mice with hypertrophy associated with compromised functionshowedsignificantup-regulationofcyclins,cyclindependent kinases (Cdks), and cell regeneration markers in myocytes. Furthermore, in human failing and nonfailing hearts, similar observations were documented including induction of active caspase 3 and Ki-67 proteins in dilated cardiomyopathic myocytes. Taken together, our data suggest that the stress of extensive myocardial damage from longstanding hypertrophy may cause myocytes to reenter the cell cycle. We demonstrate, for the first time in an animal model, that cell death and regeneration occur simultaneously in myocytes during end-stage heart failure, a phenomenon not observed at the onset of the disease process.

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Section: Figmentioning

confidence: 43%

Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

Sarkar¹,

Chawla‐Sarkar²,

Young³

et al. 2004

Journal of Biological Chemistry

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“…The Bcl-2 gene suppresses apoptosis induced by many other factors (17) and the Bax gene encodes a 21-kDa protein, and has 21% homology with the Bcl-2 gene (18). Overexpression of the Bax gene inhibits the function of Bcl-2 and promotes apoptosis (19).…”

Section: Discussionmentioning

confidence: 99%

EBP50 gene transfection promotes 5-fluorouracil-induced apoptosis in gastric cancer cells through Bax- and Bcl-2-triggered mitochondrial pathways

Dong

et al. 2012

Mol Med Report

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Abstract. 5-Fluorouracil (5-FU) plays an important role in the chemotherapy of advanced gastric cancer. However, genetic factors that affect therapeutic efficacy of 5-FU warrant further investigation. In the present study, using stable transfection of the ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) gene, we explored the genetic influences on 5-FU-induced apoptosis of human gastric cancer cells. Stable overexpression of the EBP50 gene was determined by reverse transcription polymerase chain reaction (RT-PCR) assay and western blot analysis. After treatment with 5-FU, cell growth activities in vitro were investigated by MTT assay. Cell apoptosis was evaluated by Hoechst 33258 staining and flow cytometry of Annexin V-FITC/PI staining. Compared with the BGC823 or BGC823/neo cells, EBP50 mRNA and protein levels in the BGC823/EBP50 cells (EBP50-transfected BGC823 cells) were markedly higher. Chemosensitivity and apoptosis rates of the BGC823/EBP50 cells were higher compared to the BGC823 and BGC823/neo cells following treatment with 5-FU. Stable overexpression of extrinsic EBP50 distinctly increases the 5-FU-induced apoptosis of gastric cancer cells, and is a novel strategy by which to improve the chemosensitivity of gastric cancer to 5-FU.

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“…Yet, BAX expression increases and BCL2 expression decreases during chronic experimental cardiac pressure overloading (Condorelli et al, 1999), NIX/BNIP3L is upregulated in human and experimental cardiac hypertrophy (Yussman et al, 2002;Galvez et al, 2006), and BNIP3 expression increases in ischemic cardiac models (Regula et al, 2002;Galvez et al, 2006). Recent data support a particularly important function for BNIP3 and NIX/BNIP3L in cardiomyocyte apoptosis during ventricular remodeling.…”

Section: Cardiomyocyte Apoptosis and Bcl2 Proteins In Myocardial Diseasementioning

confidence: 94%

Cardiac reanimation: targeting cardiomyocyte death by BNIP3 and NIX/BNIP3L

Dorn

Kirshenbaum

2008

Oncogene

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Programmed cardiac myocyte death contributes to pathological ventricular remodeling and the progression of myocardial infarction or pressure overload hypertrophy to dilated cardiomyopathy. Recent work has identified importance of stress-mediated transcriptional induction of BNIP3 (BCL2 and 19-kDa interacting protein-3) and NIX/BNIP3L in cardiac remodeling. Here, the regulatory mechanisms for these two factors in the heart and their effects on programmed cardiomyocyte death are reviewed, with a focus on information derived from studies using mouse models of cardiac BNIP3 and NIX/BNIP3L overexpression and gene ablation.

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Increased Cardiomyocyte Apoptosis and Changes in Proapoptotic and Antiapoptotic Genes bax and bcl -2 During Left Ventricular Adaptations to Chronic Pressure Overload in the Rat

Cited by 257 publications

References 19 publications

Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

EBP50 gene transfection promotes 5-fluorouracil-induced apoptosis in gastric cancer cells through Bax- and Bcl-2-triggered mitochondrial pathways

Cardiac reanimation: targeting cardiomyocyte death by BNIP3 and NIX/BNIP3L

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