1,721,075 research outputs found
Post-transcriptional mediators involved in cellular resistance to oxidative stress and in cellular senescence
No full text
Role of microRNAs in cellular senescence
No full textSenescence is recognized as a permanent arrest of cell proliferation triggered by telomere shortening or various stresses. Senescence imposes a barrier to tumorigenesis and contributes to aging. It represents a cell response that encompasses gene expression regulation at transcriptional and post-transcriptional levels. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that regulate diverse biological processes through their control of mRNA degradation or translation.
In this work, we have analyzed the expression profiles of 284 known microRNAs in senescent relative to early-passage IMR90 human diploid fibroblasts. We found that 179 miRNAs were expressed at significant level and that in senescent cells 47% were downregulated (at least 2-fold) and 19% were upregulated at same extent.
With only few exceptions, a similar expression profile was observed in human senescent BJ fibroblasts, as well as in young IMR90 fibroblasts treated with a mild chronic oxidative stress or with etoposide. The upregulated miRNAs, validated by Quantitative Real Time PCR, included miR-23b, miR-30e-5p, miR-126*, miR-134, miR-200c, miR-210, miR-376a*, miR-369-5p, miR-379, miR-410, miR-432, miR-485-5p, miR-486, miR-494, miR-542-5p, miR-654, miR-656 and some of them (miR-134, miR-369-3p, miR-376a*, miR-379, miR-410, miR-432, miR-485-5p, miR-494, miR-654 and miR-656) are members of an imprinted region of human chromosome 14.
We found that ectopic expression of some of the upregulated microRNAs (miR-210, miR-376a*, miR-486, miR-494, miR-542-5p, miR-654) in young proliferating IMR90 fibroblasts triggers a premature senescent phenotype showing typical markers of senescence and accompanied also by the appearance of molecular complexes involved in different patterns of DDR (DNA damage response)
Oxidative Stress and Cell Senescence Process
No full textOxidative stress due to excessive amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a leading role in damages to macromolecules and, as such, it represents a key driver of numerous physio-pathological events, including cellular senescence [...
Cellular Retinoic-acid-binding-protein and Retinol-binding-protein Messenger-rna Expression In the Cells of the Rat Seminiferous Tubules and Their Regulation By Retinoids
No full textThe levels of the mRNA corresponding to the intracellular binding proteins for retinoic acid and retinol (CRABP1 and CRBP1, respectively) were studied in primary cultures of somatic and germ cells of the rat seminiferous tubules. We show that the CRABP1 mRNA is expressed in Sertoli and germ cells and a single molecular species of mRNA is detected. CRBP1 mRNA is detected in Sertoli and peritubular cells. The regulation of the expression of both genes by retinoids was studied in Sertoli cells. CRABP1 mRNA levels are not affected by either retinoic acid or retinol, whereas both compounds positively regulate CRBP1 mRNA synthesis in a dose-dependent manner. A fivefold increase in CRBP1 mRNA levels was observed 32 - 48 h after addition of either agent. These results demonstrate that in Sertoli cells the expression of CRABP1 is not affected by retinoids, similar to the situation observed in vivo and in other in-vitro cultures. CRBP1-gene expression is, instead, induced and the variations in CRBP1-mRNA levels may regulate the intracellular concentrations of retinoids, as a response to changes in the vitamin-A nutritional status
Extinction of Retinol-binding Protein Gene-expression In Somatic Cell-hybrids - Identification of the Target Sequences
No full textThe Retinol-Binding Protein (RBP) is expressed primarily in the liver. The regulatory elements involved in its tissue-specific expression have been identified and mapped to the 5' flanking region of the RBP gene. In this paper heterokaryons and somatic cell-hybrids have been produced and analysed in order to demonstrate that the RBP gene is subject to extinction and to identify the target sequences of this phenomenon. We show here that the gene is extinguished in fusions of hepatoma with a variety of cells of different species and embryonic lineages. The repression is not due to loss of the gene and occurs also when chromosome 10, where the gene is located, is inherited from the expressing parental cell-type. Hybrid clones were transfected with constructs carrying DNa segments of different lengths from the 5' flanking region of the RBP gene fused to a reporter gene. We demonstrate that extinction takes place also on an exogenous RBP-CAT gene, mimicking the phenomenon observed with endogenous gene in its chromosomal location. Moreover, we identify and map the target sequences of the putative extinguishing function. Our data thus show that extinction of RBP is mediated through the DNA segment that is involved in its tissue-specific expression
Detection of Cellular Retinol-binding Protein Messenger-rna In the Somatic-cells of the Rat Seminiferous Tubules
No full text- …
