Drop of connexin 43 in replicative senescence of human fibroblasts HEL-299 as a possible biomarker of senescence

Statuto, Massimo; Bianchi, Cristina; Perego, R; Monte, Ugo Del

doi:10.1016/s0531-5565(02)00089-x

Cited by 27 publications

(19 citation statements)

References 32 publications

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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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“…We [13] and others [36] reported agerelated increase in adipogenic potential of satellite cells, and correlated the increased adipogenicity of satellite cells to adipose tissue development seen in sarcopenia. Interestingly, age-related decrease in Cx43 expression as well as its phosphorylation has been shown in cultured human fibroblasts [37,38] and Cx43 expression is downregulated as a function of age in most tissues in the rat [23]. Therefore, although the physiological significance of the phenotypic changes of skeletal muscle cells by AGRA treatment is unclear, it is possible that the present results represent the age-related increase in adipogenic potential of satellite cells due to a decreased Cx43 expression or phosphorylation.…”

Section: Discussionmentioning

confidence: 66%

18α-Glycyrrhetinic Acid Induces Phenotypic Changes of Skeletal Muscle Cells to Enter Adipogenesis

Yamanouchi

Yada

Ishiguro

et al. 2007

Cell Physiol Biochem

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The importance of connexins is implicated in proliferation and differentiation of cells. In skeletal muscle cells, connexin43 (Cx43) has been identified as the major connexin, and gap-junctional communication mediated by connexins has been shown to be required for their myogenic differentiation. In addition, inhibition of connexin function has been shown to induce transdifferentiation of osteoblasts to an adipocytic phenotype. In the present study, we examined whether the inhibition of connexin function could induce phenotypic changes in skeletal muscle cells. Treatment of skeletal muscle cells with an inhibitor of connexin function, 18α-glycyrrhetinic acid (AGRA), resulted in a reduction in the number of MyoD-positive cells and complete inhibition of myotube formation, concomitantly with an increase in the number of C/EBPα-positive cells. AGRA-treated cells cultured in adipogenic differentiation medium could give rise to mature adipocytes that express both PPARγ and C/EBPα. The presence of AGRA during adipogenic differentiation did not inhibit adipogenesis of skeletal muscle cells. AGRA treatment did not affect Cx43 expression in skeletal muscle cells but reduced its phosphorylation. These results indicate that inhibition of connexin function induces phenotypic changes of skeletal muscle cells to enter adipogenesis.

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“…GJIC has an important role in a variety of cellular processes, including homeostasis, morphogenesis, cell differentiation, and growth control (20,21). Statuto et al (22) reported a progressive decrease of the expression of Cx43 and GJIC in replicative senescence of cultured HEL-299 fibroblasts and termed Cx43 as a biomarker of cell senescence. It also has been shown that the expression and function of Cx43 in astrocytic cells and aortic endothelium were age related, suggesting that Cx43 and GJIC may play a role in the process of cell aging (23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Connexin 43 Expression by High Glucose Induces Senescence in Glomerular Mesangial Cells

Zhang

Chen

et al. 2006

Journal of the American Society of Nephrology

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Connexin 43 (Cx43) plays an important role in cell differentiation and growth control, but whether it can be regulated by high glucose and whether it can mediate in glomerular mesangial cells (GMC) the phenotype alterations that are induced by high glucose still remain to be explored. In this study, RNA interference and gene transfer techniques were used to knock down and overexpress Cx43 gene in rat GMC to determine the contribution of Cx43 to GMC senescence that was induced by high glucose. The results show that high glucose (30 mM) not only downregulated Cx43 mRNA and protein expression (P < 0.05) but also increased the percentage of senescence-associated ␤-galactosidase (SA-␤-gal) stained cells and expression of p21 cip1 and p27 kip1 (P < 0.05), indicating that high glucose promoted rat GMC senescence. Knocking down Cx43 gene expression significantly increased the percentage of SA-␤-gal stained cells and p27 kip1 and p21 cip1 expression in GMC (P < 0.05), whereas overexpression of Cx43 significantly decreased the percentage of SA-␤-gal stained cells (P < 0.05). These results demonstrate for the first time that downregulation of Cx43 expression by high glucose promotes the senescence of GMC, which may be involved in the pathogenesis of diabetic nephropathy.

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Drop of connexin 43 in replicative senescence of human fibroblasts HEL-299 as a possible biomarker of senescence

Cited by 27 publications

References 32 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

18α-Glycyrrhetinic Acid Induces Phenotypic Changes of Skeletal Muscle Cells to Enter Adipogenesis

Downregulation of Connexin 43 Expression by High Glucose Induces Senescence in Glomerular Mesangial Cells

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