Functional Abrogation of p53 is Required for T-Ag Induced Proliferation in Cardiomyocytes

Huh, Nam Eung; Pasumarthi, Kishore B.S.; Soonpaa, Mark H.; Jing, Shaoliang; Patton, Brian; Field, Loren J.

doi:10.1006/jmcc.2001.1403

Cited by 21 publications

(15 citation statements)

References 27 publications

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“…14,15 Although cardiac p53 expression is known to increase in several in vivo injury models (ie, myocardial infarction, 29 reperfusion injury, 30 pacing-induced heart fail- …”

Section: Discussionmentioning

confidence: 99%

“…2586 to 2452) 17 was inserted downstream from the p193 sequences. The MHC-CB7 transgene used the MHC promoter and genomic sequences comprising an 8-kb fragment of a p53 CB7 genomic clone 15,18 ( Figure 1B). The CB7 p53 allele harbors an arg to pro substitution at amino acid residue no.…”

Section: Generation Of Mhc-1152stop and Mhc-cb7 Transgenic Micementioning

confidence: 99%

“…In support of this, expression of a T antigen mutant lacking the p53 binding sites (but retaining the p193 binding site) resulted in cardiomyocyte apoptosis in transgenic mice and in ESC-derived cultures. 15 Coexpression of a dominantinterfering p53 mutant blocked mutant T antigen-induced cardiomyocyte apoptosis.…”

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confidence: 99%

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Expression of Mutant p193 and p53 Permits Cardiomyocyte Cell Cycle Reentry After Myocardial Infarction in Transgenic Mice

Nakajima

Tsai

et al. 2004

Circulation Research

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Abstract-Previous studies have demonstrated that expression of p193 and p53 mutants with dominant-interfering activities renders embryonic stem cell-derived cardiomyocytes responsive to the growth promoting activities of the E1A viral oncoproteins. In this study, the effects of p53 and p193 antagonization on cardiomyocyte cell cycle activity in normal and infarcted hearts were examined. Transgenic mice expressing the p193 and/or the p53 dominant-interfering mutants in the heart were generated. Transgene expression had no effect on cardiomyocyte cell cycle activity in uninjured adult hearts. In contrast expression of either transgene resulted in a marked induction of cardiomyocyte cell cycle activity at the infarct border zone at 4 weeks after permanent coronary artery occlusion. Expression of the p193 dominant-interfering mutant was also associated with an induction of cardiomyocyte DNA synthesis in the interventricular septa of infarcted hearts. A concomitant and marked reduction in hypertrophic cardiomyocyte growth was observed in the septa of hearts expressing the p193 dominant-interfering transgene, suggesting that cell cycle activation might partially counteract the adverse ventricular remodeling that occurs after infarction. Collectively these data suggest that antagonization of p193 and p53 activity relaxes the otherwise stringent regulation of cardiomyocyte cell cycle reentry in the injured adult heart.

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“…14,15 Although cardiac p53 expression is known to increase in several in vivo injury models (ie, myocardial infarction, 29 reperfusion injury, 30 pacing-induced heart fail- …”

Section: Discussionmentioning

confidence: 99%

Section: Generation Of Mhc-1152stop and Mhc-cb7 Transgenic Micementioning

confidence: 99%

See 1 more Smart Citation

Expression of Mutant p193 and p53 Permits Cardiomyocyte Cell Cycle Reentry After Myocardial Infarction in Transgenic Mice

Nakajima

Tsai

et al. 2004

Circulation Research

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“…These limitations can be partially circumvented by the use of pure, terminally differentiated cardiomyocyte cultures derived from embryonic stem (ES) cells 54 ; however, exploitation of this approach has been limited to date. 55,56 This latter approach is also readily amenable to cotransfection with multiple expression constructs. 55,56 In vitro gene transfer studies with positive effects on cardiomyocyte cell cycle activity are summarized ( Table 3).…”

Section: Experimental Manipulation Of Cardiomyocyte Cell Cycle Activitymentioning

confidence: 99%

“…55,56 This latter approach is also readily amenable to cotransfection with multiple expression constructs. 55,56 In vitro gene transfer studies with positive effects on cardiomyocyte cell cycle activity are summarized ( Table 3).…”

Section: Experimental Manipulation Of Cardiomyocyte Cell Cycle Activitymentioning

confidence: 99%

Cardiomyocyte Cell Cycle Regulation

Pasumarthi

Field

2002

Circulation Research

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306

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Abstract-Although rapid progress is being made in many areas of molecular cardiology, issues pertaining to the origins of heart-forming cells, the mechanisms responsible for cardiogenic induction, and the pathways that regulate cardiomyocyte proliferation during embryonic and adult life remain unanswered. In the present study, we review approaches and studies that have shed some light on cardiomyocyte cell cycle regulation. For reference, an initial description of cardiomyogenic induction and morphogenesis is provided, which is followed by a summary of published cell cycle analyses during these stages of cardiac ontology. A review of studies examining cardiomyocyte cell cycle analysis and de novo cardiomyogenic induction in the adult heart is then presented. Finally, studies in which cardiomyocyte cell cycle activity was experimentally manipulated in vitro and in vivo are reviewed. It is hoped that this compilation will serve to stimulate thought and experimentation in this intriguing area of cardiomyocyte cell biology. Key Words: cardiomyocyte proliferation Ⅲ cardiac myocyte apoptosis Ⅲ heart regeneration Ⅲ gene targeting Ⅲ transgenic mice S tudies using embryos from different species (fly, chick, zebrafish, xenopus, and mouse) have shed some light on the cardiogenic induction process. During gastrulation of the chick embryo, primitive streak cells migrate to the lateral plate mesoderm. Those cells that migrate to the anterior lateral plate mesoderm are destined to form heart tissue. [1][2][3] On migration, these cells proliferate extensively 4 while remaining in close contact with the anterior endoderm 3 (a prerequisite for their subsequent cardiomyogenic induction). 5 Recent studies have elegantly identified several growth factors that regulate cardiomyogenic induction of the precursor cells in the anterior mesoderm. These include molecules that promote cardiomyogenic induction (BMPs, FGFs, inhibitors of Wnt family of morphogens such as Crescent, Dkk-1, and glycogen synthase kinase-3), as well as molecules that inhibit the process (Wnt family of morphogens, noggin, and chordin). 6 -9 The failure of these growth factors to promote cardiomyogenic induction in more primitive precursor cells indicates that additional as of yet unidentified factors participate in the process.In contrast to our somewhat limited understanding of the inductive clues that mediate cardiomyogenic lineage determination, the morphogenetic transformation of the primitive heart into a 4-chambered structure is fairly well characterized. The heart field initially forms as a crescent shaped structure in the anterior part of the embryo that later develops into a linear tube. 10 The tubular heart undergoes segmentation along the anterior-posterior axis, followed by rightward looping. This process results in the formation of the right and left ventricles, the atrioventricular canal, the sinoatrial, and the outflow tract segments. 11,12 Subsequently, the ventral side of the heart tube rotates and forms the outer curvature of the heart, with the d...

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Reactivation of cardiomyocyte cell cycle: A potential approach for myocardial regeneration

McMullen

Gaspard

Pasumarthi

2005

Signal Transduction

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Regulation of cardiomyocyte cell cycle appears to be more complex in mammals compared to the lower vertebrates. Cardiomyocytes from the adult newt and zebrafish can proliferate in response to myocardial injury and regenerate the damaged area. In contrast, cardiomyocytes in the mammalian heart cease to proliferate soon after birth. This limits the ability of the mammalian heart to regenerate the damaged myocardium following heart disease. It is believed that increasing the number of myocytes in a diseased heart can decrease scar formation and improve myocardial function. To this end, reactivation of cell cycle in the surviving myocardium may have therapeutic value in the treatment of heart disease. Here we provide a summary of studies describing myocyte cell cycle activity during development and disease, mechanisms of cell cycle exit in the adult heart and genetic modulations affecting cardiomyocyte cell cycle activity. Further, we discuss the potential utility of myocyte cell cycle reactivation in cardiac regeneration as well as improvement of myocardial function.

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Functional Abrogation of p53 is Required for T-Ag Induced Proliferation in Cardiomyocytes

Cited by 21 publications

References 27 publications

Expression of Mutant p193 and p53 Permits Cardiomyocyte Cell Cycle Reentry After Myocardial Infarction in Transgenic Mice

Expression of Mutant p193 and p53 Permits Cardiomyocyte Cell Cycle Reentry After Myocardial Infarction in Transgenic Mice

Cardiomyocyte Cell Cycle Regulation

Reactivation of cardiomyocyte cell cycle: A potential approach for myocardial regeneration

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