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1.
Mol Cell Biochem ; 411(1-2): 117-25, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26463993

RESUMO

Cell swelling and retardation in DNA replication are always observed in senescent cells. When DNA replication is slowed down with RNA and protein syntheses unchanged in proliferating cells, it causes a phenomenon known as unbalanced growth. The purpose of this study is to assess the role of cell swelling in unbalanced growth in terms of senescence and investigate the mechanism underlying this phenomenon. We tried to induce cell swelling with minimum damage to cells in this study. We perturbed the osmoregulatory functions to induce cell swelling under hypotonic and hypertonic conditions in normal human fibroblasts. Addition of excess NaCl was found to induce significant cell and nuclear swelling in dose- and time-dependent manners. Excess NaCl immediately retarded DNA replication, accumulated cells at G1 phase of the cell cycle, and eventually deprived division potential of the cells. Such cells showed typical senescent cell shape followed by expression of the typical senescence-associated genes. Excess NaCl also activated ERK1/2, p38, and JNK of the mitogen activated protein kinase family. Addition of U0126, an inhibitor of ERK1/2, prevented appearance of senescent features induced by excess NaCl. These results suggest that hypertonic conditions induce cell swelling due to unbalanced growth, thereby leading to cellular senescence.


Assuntos
Senescência Celular/efeitos dos fármacos , Cloreto de Sódio/administração & dosagem , Linhagem Celular Transformada , Humanos , Cloreto de Sódio/farmacologia
2.
Biosci Biotechnol Biochem ; 78(12): 2022-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25198914

RESUMO

Sublethal doses of surfactants as exemplified by NP-40 clearly induce premature senescence in normal human cells. To understand molecular basis for this phenomenon, we tried to suppress it with use of various inhibitors. An inhibitor of p38 of the MAPK family almost completely suppressed growth arrest and morphological changes induced by surfactants; however, other inhibitors tested had no effect. Oleic acid, a weak inducer of premature senescence, was found to suppress the effect of NP-40. Fluorescein-labeled oleic acid rapidly bound to the cell surface, and this binding was clearly blocked by pre-treatment with surfactants, suggesting that surfactants and oleic acid compete for binding to the cell surface. Moderate concentrations of cycloheximide, an inhibitor of protein synthesis, also suppressed the senescent features induced by NP-40. These results suggest that surfactants activate p38 signaling pathway by binding to the cell surface, and induce cellular senescence.


Assuntos
Fibroblastos/efeitos dos fármacos , Imidazóis/farmacologia , Queratinócitos/efeitos dos fármacos , Octoxinol/farmacologia , Polietilenoglicóis/farmacologia , Piridinas/farmacologia , Tensoativos/farmacologia , Ligação Competitiva , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Cicloeximida/farmacologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HeLa , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Ácido Oleico/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Transdução de Sinais , beta-Galactosidase/genética , beta-Galactosidase/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
Biosci Biotechnol Biochem ; 75(7): 1395-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21737914

RESUMO

We evaluated the cytotoxicity of surfactants in human cells. Synthetic surfactants showed different cytotoxicity levels depending on their structures. The cytotoxicity of commercial washing products was determined mainly by the contents of surfactants. All of them induced premature senescence in normal cells, but not in tumor-derived or immortalized cells, under sublethal conditions. Residual surfactants might be a risk factor for skin aging.


Assuntos
Senescência Celular/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia , Tensoativos/toxicidade , Linhagem Celular , Colagenases/efeitos dos fármacos , Colagenases/metabolismo , Fibronectinas/efeitos dos fármacos , Fibronectinas/metabolismo , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Tensoativos/administração & dosagem
4.
Biogerontology ; 10(2): 213-21, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18792801

RESUMO

Pregnancy-specific glycoproteins (PSGs) comprise a family of highly similar polypeptides encoded by 11 transcriptionally active genes that compactly cluster on band 19q13.2. All members of the PSG family were found to be markedly up-regulated by addition of 5-bromodeoxyuridine in HeLa cells. Similarly, all of the members were markedly up-regulated during replicative senescence in normal human fibroblasts. Promoter analysis of the PSG1, 4, and 11 genes in HeLa cells did not reveal a cis-regulatory element responsive to 5-bromodeoxyuridine in their 5'-flanking sequences. These results suggest that the PSG genes are regulated at a level of higher order chromatin structure besides by a signal of pregnancy.


Assuntos
Proliferação de Células , Senescência Celular , Glicoproteínas beta 1 Específicas da Gravidez/metabolismo , Bromodesoxiuridina/metabolismo , Dano ao DNA , Regulação da Expressão Gênica , Genótipo , Células HeLa , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Glicoproteínas beta 1 Específicas da Gravidez/genética , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fatores de Tempo , Transfecção
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