The key role of a basic domain of histone H2B N-terminal tail in the action of 5-bromodeoxyuridine to induce cellular senescence.

5-Bromodeoxyuridine (BrdU), a thymidine analogue, is an interesting reagent that modulates various biological phenomena. BrdU, upon incorporation into DNA, causes destabilized nucleosome positioning which leads to changes in heterochromatin organization and gene expression in cells. We have previously shown that BrdU effectively induces cellular senescence, a phenomenon of irreversible growth arrest in mammalian cells.

The role of lamin B receptor in the regulation of senescence-associated secretory phenotype (SASP).

Cellular senescence is a phenomenon of irreversible growth arrest of mammalian somatic cells. Senescent cells increase the production of secretory proteins such as inflammatory cytokines, a phenomenon termed senescence-associated secretory phenotype (SASP). SASP is known to have profound effects on organismal health and aging; however, the molecular mechanisms of SASP are not precisely understood.

Extract of Plumbago zeylanica enhances the growth of hair follicle dermal papilla cells with down-regulation of 5α-reductase type II.

Background: Cellular senescence, a phenomenon of irreversible growth arrest of mammalian cells, is involved in various age-related phenomena in organisms. Hair follicle dermal papilla (DP) cells play important roles in the regulation of hair growth and loss.

Aims: We examined the implication of cellular senescence of DP cells in androgenetic alopecia (AGA), the most common form of male hair loss, and searched for the compounds that have a beneficial effect on the prevention of AGA.

Lamin B receptor plays a key role in cellular senescence induced by inhibition of the proteasome.

Cellular senescence is a terminal growth arrest phenomenon in mammalian cells. Coordinated regulation of protein synthesis and degradation is required to maintain protein homeostasis in cells; however, senescent cells exhibit decreased activity of the proteasome, a major cellular proteolytic machinery, with an accumulation of proteins. Indeed, we showed that MG132, a proteasome inhibitor, induced cellular senescence through an accumulation of proteins in human cells.

Extract of Emblica officinalis enhances the growth of human keratinocytes in culture.

Objective: Keratinocytes are the predominant cell type in the epidermis and play key roles in epidermal function. Thus, identification of the compounds that regulate the growth of keratinocytes is of importance. Here we searched for such compounds from the herbs used in traditional medicine Ayurveda.

Lamin B receptor (LBR) is involved in the induction of cellular senescence in human cells.

Cellular senescence is a phenomenon of irreversible growth arrest in mammalian somatic cells in culture. Various stresses induce cellular senescence and indeed, we have found that excess thymidine effectively induces cellular senescence in human cells. Further, many reports indicate the implication of chromatin proteins in cellular senescence.

GNG11 (G-protein subunit γ 11) suppresses cell growth with induction of reactive oxygen species and abnormal nuclear morphology in human SUSM-1 cells.

Enforced expression of GNG11, G-protein subunit γ 11, induces cellular senescence in normal human diploid fibroblasts. We here examined the effect of the expression of GNG11 on the growth of immortalized human cell lines, and found that it suppressed the growth of SUSM-1 cells, but not of HeLa cells. We then compared these two cell lines to understand the molecular basis for the action of GNG11.

Central roles of iron in the regulation of oxidative stress in the yeast Saccharomyces cerevisiae.

Oxygen is essential for aerobic organisms but causes cytotoxicity probably through the generation of reactive oxygen species (ROS). In this study, we screened for the genes that regulate oxidative stress in the yeast Saccharomyces cerevisiae, and found that expression of CTH2/TIS11 caused an increased resistance to ROS. CTH2 is up-regulated upon iron starvation and functions to remodel metabolism to adapt to iron starvation.

Triphala, a formulation of traditional Ayurvedic medicine, shows protective effect against X-radiation in HeLa cells.

Ayurveda is a holistic medical system of traditional medicine, and Triphala is one of the most popular formulations in Ayurveda. Triphala is composed of three kinds of herb, Terminalia chebula, Terminalia bellirica, and Emblica officinalis. Since Triphala is shown to exhibit a protective activity against ionizing radiation in mice, we investigated its activity in HeLa cells.

Dual roles of ERK1/2 in cellular senescence induced by excess thymidine in HeLa cells.

DNA damage response is crucially involved in cellular senescence. We have previously shown that excess thymidine, which stalls DNA replication forks, induces cellular senescence in human cells, and ERK1/2 play a key role in the induction of it. In this study, we found that Chk1 and ERK1/2 were activated to promote cell survival upon addition of excess thymidine.

Combinatorial effects of continuous protein synthesis, ERK-signaling, and reactive oxygen species on induction of cellular senescence.

Mammalian cells, when treated with sub-lethal doses of genotoxic stresses, slow down DNA synthesis but continue protein synthesis. Thus, these cells show an accumulation of proteins and undergo unbalanced growth. In the previous studies, we have shown that HeLa cells treated with excess thymidine or camptothecin undergo unbalanced growth, and prolonged unbalanced growth causes induction of cellular senescence, which is suppressed by restriction of protein synthesis or inhibition of ERK-signaling.

Aberrant localization of lamin B receptor (LBR) in cellular senescence in human cells.

5-Bromodeoxyuridine (BrdU), a thymidine analogue, induces cellular senescence in mammalian cells. BrdU induces cellular senescence probably through the regulation of chromatin because BrdU destabilizes or disrupts nucleosome positioning and decondenses heterochromatin. Since heterochromatin is tethered to the nuclear periphery through the interaction with the nuclear envelope proteins, we examined the localization of the several nuclear envelope proteins such as lamins, lamin-interacting proteins, nuclear pore complex proteins, and nuclear transport proteins in senescent cells.

Restriction of protein synthesis abolishes senescence features at cellular and organismal levels.

Cellular senescence or its equivalence is induced by treatment of cells with an appropriate inducer of senescence in various cell types. Mild restriction of cytoplasmic protein synthesis prevented induction of all aspects of cellular senescence in normal and tumor-derived human cells. It allowed the cells to continuously grow with no sign of senescent features in the presence of various inducers.

High concentrations of NaCl induce cell swelling leading to senescence in human cells.

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.

ERK1/2 mediates unbalanced growth leading to senescence induced by excess thymidine in human cells.

Excess thymidine induces unbalanced growth by delaying DNA replication and subsequently induces senescence in every human cell type. Our previous studies with use of inhibitors suggested that ERK1/2 has a major role in these processes. Here we directly assessed the roles of ERK1 and ERK2 in unbalanced growth induced by excess thymidine.

Systematic screen for genes involved in the regulation of oxidative stress in the nematode Caenorhabditis elegans.

Oxygen is essential for animals, but high concentrations of oxygen are toxic to them probably because of an increase in reactive oxygen species (ROS). Many genes are involved in the regulation of ROS, but they largely remain to be identified. To identify these genes, we employed the nematode Caenorhabditis elegans as a model organism, and systematically screened for genes that, when down-regulated by RNAi, lead to an increased sensitivity to ROS.

A mutation in a mitochondrial dehydrogenase/reductase gene causes an increased sensitivity to oxidative stress and mitochondrial defects in the nematode Caenorhabditis elegans.

rad-8 is an interesting mutant that shows increased sensitivities to UV radiation and reactive oxygen species in the nematode Caenorhabditis elegans. In this study, we have characterized rad-8 and have found that rad-8 showed several phenotypes of mitochondrial dysfunction such as a decreased activity of the respiratory chain, increased generation of superoxide anions, increased oxidative damage, increased apoptosis, and abnormal mitochondrial structure. Our genetic analysis has also indicated that rad-8 has a causative mutation in the F56H1.

Sublethal doses of surfactants induce premature senescence in normal human skin cells.

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.

N-terminal short fragment of TUP1 confers resistance to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae.

Small molecules that exhibit biological activity have contributed to the understanding of the molecular mechanisms of various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analogue that modulates various biological phenomena such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to function through changing chromatin structure and gene expression, its precise molecular mechanisms are not understood.

Mutation in a mitochondrial ribosomal protein causes increased sensitivity to oxygen with decreased longevity in the nematode Caenorhabditis elegans.

Oxygen is essential for animals, but high concentrations of oxygen are toxic to them probably because of an increase in reactive oxygen species (ROS). Many genes are involved in the reactions from which ROS are generated, but not much attention has been focused on them. To identify these genes, we screened for mutants with an altered sensitivity to oxidative stress in the nematode Caenorhabditis elegans and isolated a mutant, oxy-5(qa5002).

5-bromodeoxyuridine induces transcription of repressed genes with disruption of nucleosome positioning.

5-Bromodeoxyuridine (BrdU) modulates the expression of particular genes associated with cellular differentiation and senescence when incorporated into DNA instead of thymidine (dThd). To date, a molecular mechanism for this phenomenon remains a mystery in spite of a large number of studies. Recently, we have demonstrated that BrdU disrupts nucleosome positioning on model plasmids mediated by specific AT-tracts in yeast cells.

Identification of genes that affect sensitivity to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae.

Small molecules that exhibit biological effects have been successfully used to study various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analog that affects various biological processes, such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to modulate these phenomena by changing chromatin structure and gene expression, the molecular mechanisms for the action of BrdU are not understood well.

[FeFe]-hydrogenase-like gene is involved in the regulation of sensitivity to oxygen in yeast and nematode.

Oxygen is essential for the life of aerobic organisms, but reactive oxygen species (ROS) derived from oxygen can be a threat for it. Many genes are involved in generation of ROS, but not much attention has been focused on the reactions from which ROS are generated. We therefore screened for mutants that showed an increased sensitivity to oxidative stress in the nematode Caenorhabditis elegans, and isolated a novel mutant, oxy-4(qa5001).