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The stress-inducible immediate early response gene X-1 (IEX-1) regulates cell proliferation and apoptosis in a cell type and stimulus-dependent manner. The aim of this study was to investigate IEX-1 expression in preeclampsia placenta and human umbilical vein endothelial cells (HUVECs) cultured in the serum isolated from preeclampsia patients, to explore its relationship with the pathogenesis of preeclampsia. Thirty preeclampsia patients with 10 cases in the moderate group, 20 cases in the severe group (PE group) and 20 cases of normal pregnant women (control group) were randomly obtained. Reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that IEX-1 expression was significantly higher in preeclampsia patients than in normal pregnant women ( p < 0.05). There was also a significant difference between moderate and severe preeclampsia ( p < 0.05). IEX-1 protein was mainly present in cytoplasm of placental trophoblast cells and decidual cells. Compared with the normal pregnancy group, IEX-1 in the preeclampsia group was colored more obviously, and the color was strengthened in correlation with the severity of the disease using immunocytochemial method. Flow cytometry and MTT revealed that the serum isolated from preeclampsia patients appeared to promote IEX-1 expression in cytoplasm of HUVECs, inhibited the proliferation and promoted the apoptosis of HUVECs when compared to the serum of normal pregnant women. Our study demonstrates a correlation of IEX-1 expression levels with the severity of preeclampsia. Given a well-known function of IEX-1 in regulation of apoptosis, IEX-1 may be important in the pathogenesis of preeclampsia by regulating placental villous trophoblast and decidual cell apoptosis as well as participation in endothelial cell injury process. [ABSTRACT FROM AUTHOR]

Failure to execute an apoptotic programme is one of the critical steps and a common mechanism promoting tumorogenesis. Immediate early responsive gene 3 (IER3) has been shown to be upregulated in several cancers. IER3 is a stress-induced gene, which upregulation leads to reduction in production of reactive oxygen species (ROS) protecting malignant cells from apoptosis. We observed that malignant lymphocytes from patients with Sézary syndrome (SzS) were resistant to pro-apoptotic dose of tumour necrosis factor-α (TNF-α). The aim of this study was to investigate the role of IER3 in the mechanism of such resistance. CD4+ CD26− lymphocytes from the peripheral blood of patients with SzS and healthy controls were negatively selected using CD4 and CD26 magnetic beads and analysed for expression of TNFR1, TNFR2, IER3 expression, and ROS production in response to TNF-α at an apoptotic dose. Sézary cells with a higher level of IER3 expression retained their viability to TNF-α. IER3 upregulation correlated with a decrease level of intracellular ROS and low TNFR1 expression on malignant cells. Targeting IER3 could be of interest for the development of future therapeutic strategies for patients with SzS. [ABSTRACT FROM AUTHOR]

Background: The stress-inducible immediate early response gene X-1 (IEX-1) regulates cell proliferation and apoptosis in a cell type and stimulus-dependent manner. The aim of this study was to investigate IEX-1 expression and its role in apoptosis of ovarian epithelial tumors for potential use in clinical diagnosis and therapy. Methods: IEX-1 expression was examined in paraffin-embedded specimens from 77 patients with epithelial ovarian tumors using immunohistochemistry. Correlation between IEX-1 expression and other clinicopathological parameters was evaluated. Apoptosis of tumor cells was detected by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL). Results: IEX-1 expression was significantly lower in ovarian cancers compared to cystadenomas and borderline tumors ( p < .05). The expression was significantly associated with FIGO stage and histological grade ( p < .05), but not with age, histological type, or residual tumor ( p > .05). A positive correlation was also observed between IEX-1 expression and apoptotic index ( p < .01) or survival ( p == .005). Conclusion: With the development of epithelial ovarian tumors from benign to malignant, IEX-1 expression is decreased, concomitant with a decreased rate of cell apoptosis. Thus, IEX-1 is pro-apoptotic in the development of epithelial ovarian cancer. The pro-apoptotic activity may take part in restraining tumor growth at the early stage of ovarian epithelial cancer, whereas its decreased expression probably contributes to the abnormal survival advantage for malignant cancer. Altered IEX-1 expression can potentially be a new predictor of the malignant transformation and a prognostic indicator for cancer therapy. [ABSTRACT FROM AUTHOR]

Provides information on a study that examined how transcription factors Nf-κB/rel proteins, p53 and c-Myc coordinarily control immediate early response gene X-1 expression. Results and discussion; Materials and methods used.

Abstract: An altered redox status and increased lymphocyte apoptosis have been implicated in the development of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between glutathione (GSH) depletion, reactive oxygen species (ROS) and, the progression of apoptosis and their association with SLE severity. Significant low levels of intracellular glutathione, total thiol and altered redox state (GSH/GSSG) were found in SLE patients, in which lymphocyte apoptosis and activated caspase-3 expression in the lymphocytes were remarkably increased. The severity of disease was positively allied with the increased levels of lymphocyte apoptosis and caspase-3, but negatively with the decreased levels of total thiol, depleted intracellular glutathione and altered redox state (GSH/GSSG). The lymphocyte apoptosis and activated caspase-3 expression were negatively associated with intracellular levels of GSH and redox state and positively associated with the elevated levels of multiple oxidative stress markers; ROS and lipid peroxidation measured as malondialdehyde (MDA). These results suggest that GSH depletion and elevated oxidative stress trigger apoptosis and may be coupled with the severity of the disease. [Copyright &y& Elsevier]