Search

This study aims to determine if genetic polymorphisms in the HLA‐G gene are associated with age‐related macular degeneration (AMD). HLA‐G is important for immunological tolerance, and it is also known to have angiogenic effects. Polymorphisms in the 5′‐upstream regulatory region and 3′‐untranslated region (UTR) of HLA‐G have been associated with a number of diseases, especially with respect to a 14 bp insertion/deletion (ins/del) polymorphism in the 3′UTR. Full gene sequencing was performed on a cohort of 146 AMD patients and 63 healthy controls aged ≥60 and HLA‐G haplotypes were determined. Analyses were performed on a publicly available gene expression dataset from the NCBI GEO database (accession number GSE29801) from which expression data for HLA‐G, ‐C, and ‐A were extracted. Analysis of the GEO dataset showed that both HLA‐G and ‐C were expressed in the back of the eye and that expression was upregulated in the macular area of AMD. No differences were observed between patients and controls when analyzing the distribution of haplotypes in the HLA‐G promoter, coding region, 3′UTR, or the 14 bp ins/del polymorphism of the 3′UTR. The increased expression of HLA‐G in the macula of AMD patients indicates a role of HLA‐G in the micro environment as part of the AMD pathogenesis. This is supported by the expression of HLA‐C, which has previously been shown to play a role in AMD. The HLA‐G haplotype distribution did not display any differences between AMD patients and controls. [ABSTRACT FROM AUTHOR]

Purpose: To examine the influence of dose, dose-rate and radiation quality on telomerase activity (TA) in the KG1a hematopoietic cell line. Materials and methods: KG1a cells were irradiated with γ-rays (0.5-5 Gy) at 0.025 Gy/min, 0.30 Gy/min and 1.57 Gy/min and with a neutron/γ-ray field (5 Gy). Cell viability was determined by trypan blue exclusion. Apoptosis and cell cycle distribution were evaluated by flow cytometry. Proliferative capacity was studied by MTS assay and TA by PCR. Following 3Gy γ-irradiation, the expression of hTERT, hTR and TP1 genes was evaluated by RT-PCR. Results: Dose- and dose-rate-dependent telomerase activation with an increase in hTERT mRNA and a drop in hTP1 mRNA were observed after irradiation. Down-regulation of telomerase activity occurred in a dose-dependent manner. Although non-significant changes in short-term survival were observed after irradiation, late apoptosis became evident after G2/M arrest. Early repression of TA preceded telomerase activation in samples irradiated with a neutron/γ-ray field, in which short-term survival was affected. Conclusions: Radiation-induced telomerase activation depends on dose-rate. High-LET and low-LET irradiations induce similar changes in TA that differ mainly in their kinetics and their magnitude. Changes in TA are not related to cell-cycle redistribution nor to the induction of cell death; they are the consequence of specific regulatory responses to ionizing radiation. Mechanisms including both transcriptional and post-translational control may be involved in this regulation. [ABSTRACT FROM AUTHOR]

Data are presented on the intracellular trafficking of HLA-G protein, taking the unique features of this non-classical molecule into consideration: the existence of seven isoforms resulting from alternative splicing (HLA-G1 to G7), and reduced tail length compared with HLA class I antigens. Biochemical studies and analysis of viral strategies for escaping the host immune system led to the demonstration that (i) both the membrane-bound (HLA-G1) and the soluble (HLA-G5) forms of the molecule require peptide association for cell surface expression, using TAP-dependent or TAP-independent pathways; (ii) peptide loading onto the HLA-G protein plays a critical role in controlling the quality of the molecule reaching the cell surface; (iii) surface expression of truncated HLA-G molecules is possible, and (iv) HLA-G expression may be restricted to soluble HLA-G5. These data reveal that HLA-G presents specific cell trafficking pathways and strongly support the contention that the primary function of HLA-G is as of an inhibitor ligand for immune-competent cells. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a disorder of human pregnancy occuring in 5-10 % of all births, and represents the leading cause of infant morbidity and mortality and maternal death. In pre-eclampsia, invasion of fetal trophoblasts into maternal arteries during early pregnancy is shallow or absent. Here we examined the hypothesis that HLA-G, a non-classical class I HLA expressed in cytotrophoblasts, may act as a key gene in pre-eclampsia. We analysed HLA-G at the level of transcription and genotyped a silent CAC-CAT polymorphism in exon 3 and a 14-bp insertion/deletion in the 3′ untranslated region. A deficit in levels of the HLA-G3 transcript was observed in mild pre-eclampsia compared to normal placentas. The distribution of HLA-G polymorphisms was different between normal and pre-eclampsia samples. A correlation between the alteration in transcription of the HLA-G gene and certain HLA-G genotypes was also observed. Thus we provide the first evidence for a possible role of HLA-G in genetic susceptibility to, and pathogenesis of pre-eclampsia. [ABSTRACT FROM AUTHOR]

X-ray treatment induces a complex molecular response in hematopoietic cells leading to cell death. Using the mRNA differential display technique, we searched for genes whose expression was modified by ionizing radiation (IR) in the human p53-deficient leukemic cell line KG1a. We isolated a partial cDNA corresponding to the interferon (IFN)-inducible 1-8d gene. The expression of both 1-8d and 9-27, another gene from the same IFN-inducible family, was increased 24 and 48 h following irradiation. We did not find enhancement of either IFNgamma mRNA or interferon regulatory factor-1 (IRF-1) mRNA in irradiated KG1a cells, indicating that 1-8d and 9-27 enhancement was not due to an IFN activation. Thus, the induction of IFN-inducible genes by IR may provide a link between radiation-induced and IFN-mediated cell death. [ABSTRACT FROM AUTHOR]

Telomeric DNA protects chromosome ends from recombination events and its length serves as a mitotic clock that triggers exit from the cell cycle when telomeres become too short. Telomerase is the enzyme involved in telomere elongation, one of the events that permits unlimited cell proliferation. Variations in telomerase activity were quantified in hematopoietic cell lines after gamma-irradiation. Telomerase activity increased after irradiation of between 0 and 3 Gy in a dose-dependent manner, reaching a maximum at 3 Gy. The increase in telomerase activity was nearly maximum 8 h after irradiation, the peak being observed at around 24 h. Although this kinetics partly correlated with cell redistribution into the G2/M phase of the cell cycle, telomerase activity did not show significant variation over the cell cycle. Therefore, the activation of telomerase observed after gamma-irradiation may suggest the involvement of telomerase in DNA repair and chromosome healing. [ABSTRACT FROM AUTHOR]