Localization of proliferating cell nuclear antigen in the developing and mature rat heart cell

Marino, Thomas A.; Cao, Wei; Lee, Joshua; Courtney, Richard J.

doi:10.1002/(sici)1097-0185(199608)245:4<677::aid-ar8>3.0.co;2-l

Cited by 14 publications

(5 citation statements)

References 38 publications

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“…5,21 Western blotting of the housekeeping protein ␤-tubulin (monoclonal antibody kindly provided by Dr Zhonglin Chai, Baker HRI, Victoria, Australia) was also performed to demonstrate equal loading of the protein samples.…”

Section: Determination Of Cardiac Fibroblast Function and Mmp Activitymentioning

confidence: 99%

Relaxin Reverses Cardiac and Renal Fibrosis in Spontaneously Hypertensive Rats

et al. 2005

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Abstract-The antifibrotic effects of the peptide hormone relaxin on cardiac and renal fibrosis were studied in 9-to 10-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Rats (nϭ8 to 9 per group) were allocated into 3 groups: WKY controls, vehicle-treated SHR (SHR-V), and relaxin-treated SHR (SHR-R). Relaxin (0.5 mg/kg per day) was administered via subcutaneously implanted osmotic mini-pumps over 2 weeks before hearts and kidneys were harvested for analysis. Collagen content was analyzed by hydroxyproline assay, gel electrophoresis, and quantitative histology. Zymography was used to determine matrix metalloproteinase (MMP) expression and Western blotting to determine proliferating cell nuclear antigen (PCNA) expression and ␣-smooth muscle actin (␣-SMA)/myofibroblast expression, whereas cardiac hypertrophy was assessed by myocyte size and real-time polymerase chain reaction of associated genes.

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Section: Determination Of Cardiac Fibroblast Function and Mmp Activitymentioning

confidence: 99%

Relaxin Reverses Cardiac and Renal Fibrosis in Spontaneously Hypertensive Rats

et al. 2005

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“…The PCNA protein was located at nuclei, and the cells with intense brown nuclear staining were considered positive for PCNA expression. Ten random fields per section were analyzed and the average values of the PCNA positive cell percentages were calculated [14], [15].…”

Section: Detection Of Proliferating Cell Nuclear Antigen (Pcna) Exprementioning

confidence: 99%

“…The total collagen volume fraction was determined based on the Hp concentration in the left ventricles [13]. Proliferating cell nuclear antigen (PCNA) is a 36 kDa acidic, non-histone, nuclear protein required for DNA synthesis, and can be considered as a marker of cell proliferation [14], [15]. The results showed that the Hp concentration and the nuclear expression of PCNA were significantly increased in the AC group, while treatment with EGCG 50 and 100 mg/kg for 6 weeks remarkably reduced the Hp concentration (• " Fig.…”

mentioning

confidence: 99%

EGCG Inhibits Proliferation of Cardiac Fibroblasts in Rats with Cardiac Hypertrophy

Sheng¹,

Z²,

Xie³

et al. 2008

Planta Med

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This study was carried out in order to investigate the effects of epigallocatechin gallate (EGCG) on myocardial fibrosis and cell proliferation in cardiac hypertrophy. Cardiac hypertrophy was established in rats by abdominal aortic constriction, and EGCG at doses of 25, 50 and 100 mg/kg was administered intragastrically for 6 weeks. The results showed that in the rats with cardiac hypertrophy, EGCG at 25 - 100 mg/kg dose-dependently reduced heart weight indices, decreased atrial natriuretic polypeptide and endothelin levels in plasma, but increased nitrite (the oxidative product of NO) levels in the serum and in the myocardium. EGCG also reduced the hydroxyproline concentration and decreased the proliferating cell nuclear antigen expression in the hypertrophic myocardium. EGCG remarkably inhibited pressure overload-induced c-myc increase in Western blot analysis. In cultured newborn rat cardiac fibroblasts, treatment with EGCG at 12.5 - 200 mg/L for 6 - 48 h decreased cell proliferation induced by serum. EGCG at 12.5 - 100 mg/L dose-dependently inhibited cell proliferation and DNA synthesis of fibroblasts induced by angiotensin II (Ang II) at 1 mumol/L. EGCG also significantly increased nitrite levels in culture medium, and up-regulated inducible nitric oxide synthase protein expression if compared with the Ang II group. The inhibitory effect of EGCG on cell proliferation induced by Ang II was partly blocked by pretreatment with N(omega)-nitro- L-arginine methyl ester hydrochloride. These results suggest that EGCG inhibits the proliferation of cardiac fibroblasts both in vivo and in vitro, thereby preventing myocardial fibrosis in cardiac hypertrophy. EGCG might exert its cardiac protective action through induction of NO production.

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“…Since CMs exit the cell cycle soon after birth, it is imperative to know the fate of these major DNA replication proteins in the adult heart cells. Although, previous studies have demonstrated down-regulation of DNA replication proteins in the adult heart [12] , [13] , [14] , however, whether the expression of RFC and Pol δ proteins are down-regulated in adult normal CMs and CFs is still elusive. In this study, we show that transcription of RFC40 gene and translation of the catalytic subunit of Pol δ protein, p125, are suppressed in the normal adult CMs.…”

Section: Introductionmentioning

confidence: 98%

Down-Regulation of Replication Factor C-40 (RFC40) Causes Chromosomal Missegregation in Neonatal and Hypertrophic Adult Rat Cardiac Myocytes

et al. 2012

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BackgroundAdult mammalian cardiac myocytes are generally assumed to be terminally differentiated; nonetheless, a small fraction of cardiac myocytes have been shown to replicate during ventricular remodeling. However, the expression of Replication Factor C (RFC; RFC140/40/38/37/36) and DNA polymerase δ (Pol δ) proteins, which are required for DNA synthesis and cell proliferation, in the adult normal and hypertrophied hearts has been rarely studied.MethodsWe performed qRT-PCR and Western blot analysis to determine the levels of RFC and Pol δ message and proteins in the adult normal cardiac myocytes and cardiac fibroblasts, as well as in adult normal and pulmonary arterial hypertension induced right ventricular hypertrophied hearts. Immunohistochemical analyses were performed to determine the localization of the re-expressed DNA replication and cell cycle proteins in adult normal (control) and hypertrophied right ventricle. We determined right ventricular cardiac myocyte polyploidy and chromosomal missegregation/aneuploidy using Fluorescent in situ hybridization (FISH) for rat chromosome 12.ResultsRFC40-mRNA and protein was undetectable, whereas Pol δ message was detectable in the cardiac myocytes isolated from control adult hearts. Although RFC40 and Pol δ message and protein significantly increased in hypertrophied hearts as compared to the control hearts; however, this increase was marginal as compared to the fetal hearts. Immunohistochemical analyses revealed that in addition to RFC40, proliferative and mitotic markers such as cyclin A, phospho-Aurora A/B/C kinase and phospho-histone 3 were also re-expressed/up-regulated simultaneously in the cardiac myocytes. Interestingly, FISH analyses demonstrated cardiac myocytes polyploidy and chromosomal missegregation/aneuploidy in these hearts. Knock-down of endogenous RFC40 caused chromosomal missegregation/aneuploidy and decrease in the rat neonatal cardiac myocyte numbers.ConclusionOur novel findings suggest that transcription of RFC40 is suppressed in the normal adult cardiac myocytes and its insufficient re-expression may be responsible for causing chromosomal missegregation/aneuploidy and in cardiac myocytes during right ventricular hypertrophy.

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Localization of proliferating cell nuclear antigen in the developing and mature rat heart cell

Cited by 14 publications

References 38 publications

Relaxin Reverses Cardiac and Renal Fibrosis in Spontaneously Hypertensive Rats

Relaxin Reverses Cardiac and Renal Fibrosis in Spontaneously Hypertensive Rats

EGCG Inhibits Proliferation of Cardiac Fibroblasts in Rats with Cardiac Hypertrophy

Down-Regulation of Replication Factor C-40 (RFC40) Causes Chromosomal Missegregation in Neonatal and Hypertrophic Adult Rat Cardiac Myocytes

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