Modulation of Gap Junctions in Senescent Endothelial Cells

Xie, Han-qing; Hu, Valerie W.

doi:10.1006/excr.1994.1246

Cited by 61 publications

(35 citation statements)

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“…Relatively less is known about how gap junctions are involved in the control of cell death. Reduced gap junction cell-cell communication and down-regulated expression of Cx43 were reported in the senescent endothelial cells [12] and in the senescent human fibroblasts [11]. The current results support the previous findings.…”

Section: Discussionsupporting

confidence: 91%

“…Intercellular communication through gap junctions has long been known to play an important role in cell proliferation, as well as in cell differentiation [9,10]. Several lines of evidence suggested that gap junctions are defective in replicative senescent human cells [11,12]. In this work, changes of gap junctions were investigated in the study of the drug-induced premature senescence.…”

Section: Introductionmentioning

confidence: 99%

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Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

2004

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To examine the role of gap junctions in cell senescence, the changes of gap junctions in cisplatin-induced premature senescence of primary cultured fibroblasts were studied and compared with the replicative senescent human fibroblasts. Dye transfer assay for gap junction function and immunofluorescent staining for connexin 43 protein distribution were done respectively. Furthermore, cytofluorimetry and DAPI fluorescence staining were performed for cell cycle and apoptosis analysis. p53 gene expression level was detected with indirect immunofluorescence. We found that cisplatin (10 mM) treatment could block cell growth cycle at G1 and induced premature senescence. The premature senescence changes included high frequency of apoptosis, elevation of p53 expression, loss of membranous gap junctions and reduction of dye-transfer capacity. These changes were comparable to the changes of replicative senescence of human fibroblasts. It was also concluded that cisplatin could induce premature senescence concomitant with inhibition of gap junctions in the fibroblasts. Loss of functional gap junctions from the cell membrane may account for the reduced intercellular communication in the premature senescent fibroblasts. The cell system we used may provide a model useful for the study of the gap junction thus promoting agents against premature senescence.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

2004

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“…This parameter has been decreased also in senescent human endothelial cells [151]. The levels of connexin 42 messenger RNA and protein decline were revealed as these cells age in vitro.…”

Section: Cellular Senescence and Carcinogenesismentioning

confidence: 88%

“…The levels of connexin 42 messenger RNA and protein decline were revealed as these cells age in vitro. The inability of senescent cells to down-regulate gap junctions in response to epidermal growth factor reflect a defect in the regulatory mechanism of gap junction activity in senescent cells [151].…”

Section: Cellular Senescence and Carcinogenesismentioning

confidence: 99%

The relationship between aging and carcinogenesis: a critical appraisal

Anisimov

2003

Critical Reviews in Oncology/Hematology

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The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by several mechanisms: (1) tissue accumulation of cells in late stages of carcinogenesis; (2) alterations in homeostasis, in particular, alterations in immune and endocrine system and (3) telomere instability linking aging and increased cancer risk. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Available evidence supporting the relevance of replicative senescence of human cells and telomere biology to human cancer seems quite strong, however, the evidence linking cellular senescence to human aging is controversial and required additional stuidies. Data on the acceleration of aging by carcinogenic agents as well as on increased cancer risk in patients with

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“…Although our finding that connexins 43, 40, and 37 are expressed in arterial endothelial cells of different vessels is in keeping with earlier observations (Little et al 1995a;Reed et al 1993;Pepper et al 1992), the immunolocalization results we report here differ from and extend previous studies in several significant respects. Connexin43 has been reported to be expressed in cultured endothelial cells derived from a variety of vessel types and species (e.g., brain microvascular system, umbilical vein, pulmonary artery and aorta) from both Northern blot and immunofluorescence studies (Carter et al 1996;Xie and Hu 1994;Pepper et al 1992;Larson et al 1990). …”

Section: Discussionmentioning

confidence: 99%

Gap Junction Localization and Connexin Expression in Cytochemically Identified Endothelial Cells of Arterial Tissue

Yeh

Dupont

Coppen

et al. 1997

J Histochem Cytochem.

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S U M M A R Y Vascular endothelial cells interact with one another via gap junctions, but information on the precise connexin make-up of endothelial gap junctions in intact arterial tissue is limited. One factor contributing to this lack of information is that standard immunocytochemical methodologies applied to arterial sections do not readily permit unequivocal localization of connexin immunolabeling to endothelium. Here we introduce a method for multiple labeling with specific endothelial cell markers and one or more connexin-specific antibodies which overcomes this limitation. Applying this method to localize connexins 43, 40, and 37 by confocal microscopy, we show that the three connexin types have quite distinctive labeling patterns in different vessels. Whereas endothelial cells of rat aorta and coronary artery characteristically show extensive, prominent connexin40, and heterogeneous scattered connexin37, the former, unlike the latter, also has abundant connexin43. The relative lack of connexin43 in coronary artery endothelium was confirmed in both rat and human using three alternative antibodies. In the aorta, connexins43 and 40 commonly co-localize to the same junctional plaque. Even within a given type of endothelium, zonal variation in connexin expression was apparent. In rat endocardium, a zone just below the mitral valve region is marked by expression of greater quantities of connexin43 than surrounding areas. These results are consistent with the idea that differential expression of connexins may contribute to modulation of endothelial gap junction function in different segments and subzones of the arterial system. ( J Histochem Cytochem 45:539-550, 1997)The vascular endothelium forms a continuous monolayer lining the luminal surface of the entire cardiovascular system, providing the structural and metabolic interface between the blood and underlying tissues. Endothelial integrity is essential for maintenance of healthy tissue function, and perturbations of endothelial structure and function are critical to the pathogenesis of vascular disease (Ross 1995;Stary et al. 1994). Integration of endothelial cell functions is mediated by a variety of intercellular signaling mechanisms, including direct cell-to-cell communication via gap junctions (Larson 1988). Gap junctions are specialized cell membrane domains consisting of clusters of protein channels that link the cytoplasmic compartments of neighboring cells, forming pathways for direct exchange of ions and small molecules (for reviews see Yamasaki and

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Modulation of Gap Junctions in Senescent Endothelial Cells

Cited by 61 publications

References 0 publications

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

The relationship between aging and carcinogenesis: a critical appraisal

Gap Junction Localization and Connexin Expression in Cytochemically Identified Endothelial Cells of Arterial Tissue

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