Hyun-Jung Kim

Redox regulation of PTEN and protein tyrosine phosphatases in H2O2-mediated cell signaling

Protein tyrosine phosphatase (PTP) is a family of enzymes important for regulating cellular phosphorylation state. The oxidation and consequent inactivation of several PTPs by H2O2 are well demonstrated. It is also shown that recovery of enzymatic activity depends on the availability of cellular reductants. Among these redox‐regulated PTPs, PTEN, Cdc25 and low molecular weight PTP are known to form a disulfide bond between two cysteines, one in the active site and the other nearby, during oxidation by H2O2. The disulfide bond likely confers efficiency in the redox regulation of the PTPs and protects cysteine‐sulfenic acid of PTPs from further oxidation. In this review, through a comparative analysis of the oxidation process of Yap1 and PTPs, we propose the mechanism of disulfide bond formation in the PTPs.

Syndecan-2 regulates cell migration in colon cancer cells through Tiam1-mediated Rac activation

Expression of the cell surface adhesion receptor syndecan-2 is known to be involved in the regulation of cancer cell migration. However, the molecular mechanism of syndecan-2-mediated cell migration remains unknown. Here we report that Rac contributes to the regulation of syndecan-2-mediated cancer cell migration. Overexpression of syndecan-2 enhanced migration and invasion of human colon adenocarcinoma cells Caco-2 and HCT116 cells. In parallel with the increased cell migration/invasion, syndecan-2 overexpression enhanced Rac activity, while dominant negative Rac (RacN17) diminished syndecan-2-mediated increased cancer cell migration. In addition syndecan-2 expression increased membrane localization of Tiam1 and syndecan-2-mediated cell migration/invasion of Caco-2 cells was diminished when Tiam1 levels were knocked-down with small inhibitory RNAs. Furthermore, oligomerization-defective syndecan-2 mutants failed to increase membrane localization of Tiam1, activation of Rac and subsequent cell migration of both Caco-2 and HCT116 cells. Taken together, these results suggest that syndecan-2 regulates cell migration of colon carcinoma cells through Tiam1-dependent Rac activation in colon cancer cells.

SUMO1 attenuates stress-induced ROS generation by inhibiting NADPH oxidase 2

Small ubiquitin-like modifier 1 (SUMO1) is a member of the superfamily of ubiquitin-like proteins. Despite its structural similarity with ubiquitin, SUMO1 does not seem to play any role in protein degradation and its precise biological function is poorly understood. During our studies on heat-shock responses, we found that heat-shock stress increased SUMO1 conjugation in a dose-dependent manner. Intriguingly, SUMO1 conjugation resulted in decrease of intracellular ROS generation and protection cells from death under heat-shock stress. We showed that NADPH oxidase 2 (NOX2) is a target protein of sumoylation by SUMO1 using immunoprecipitation and is colocalized with SUMO1 at plasma membrane. Additionally, we demonstrated that the attenuation in intracellular ROS generation resulted from inhibition of NADPH oxidase complex (NOX) activity. These results suggested that SUMO1 plays an important role in modulation of NOX activity required for ROS generation.

Optimization of cluster-based evolutionary undersampling for the artificial neural networks in corporate bankruptcy prediction

We examined the effectiveness an optimized cluster-based undersampling technique.We used a GA-based optimization approach for selecting the appropriate instances.A critical issue of real-world knowledge extraction is the data imbalance problem.The proposed method is successfully applied to the bankruptcy prediction problem. We suggest an optimization approach of cluster-based undersampling to select appropriate instances. This approach can solve the data imbalance problem, which can lead to knowledge extraction for improving the performance of existing data mining techniques. Although data mining techniques among various big data analytics technologies have been successfully applied and proven in terms of classification performance in various domains, such as marketing, accounting and finance areas, the data imbalance problem has been regarded as one of the most important issues to be considered.We examined the effectiveness of a hybrid method using a clustering technique and genetic algorithms based on the artificial neural networks model to balance the proportion between the minority class and majority class. The objective of this paper is to constitute the best suitable training dataset for both decreasing data imbalance and improving the classification accuracy. We extracted the properly balanced dataset composed of optimal or near-optimal instances for the artificial neural networks model. The main contribution of the proposed method is that we extract explorative knowledge based on recognition of the data structure and categorize instances through the clustering technique while performing simultaneous optimization for the artificial neural networks modeling. In addition, we can easily understand why the instances are selected by the rule-format knowledge representation increasing the expressive power of the criteria of selecting instances. The proposed method is successfully applied to the bankruptcy prediction problem using financial data for which the proportion of small- and medium-sized bankruptcy firms in the manufacturing industry is extremely small compared to that of non-bankruptcy firms.

N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinsons disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD.

Association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer

Objective Decreased adiponectin and increased leptin plasma concentrations are believed to be associated with the occurrence and progression of cancers such as endometrial cancer and breast cancer. The aim of this study was to explore the association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer. Methods For patients with ovarian cancer and the control group, adiponectin and leptin levels were measured; anthropometric data were obtained during a chart review. Statistical comparisons between groups were analyzed using the Students t-test; correlations were confirmed using the Pearson correlation. Results The mean adiponectin and leptin concentrations in patients with ovarian cancer were lower than those of the control group (8.25 vs. 11.44 µg/mL, respectively; P=0.026) (7.09 vs. 15.4 ng/mL, respectively; P=0.001). However, there was no significant difference in adiponectin and leptin levels between early-stage (I/II) and advanced-stage (III/IV) disease (P=0.078). Conclusion Compared with other gynecological cancers, the level of adiponectin and leptin were decreased in ovarian cancer that may have some diagnostic value; additional study to elucidate the function of these two hormones in the development of ovarian carcinogenesis is necessitated.

Support Vector Machines Approach to Pattern Detection in Bankruptcy Prediction and Its Contingency

This study investigates the effectiveness of support vector machines (SVM) approach in detecting the underlying data pattern for the corporate failure prediction tasks. Back-propagation neural network (BPN) has some limitations in that it needs a modeling art to find an appropriate structure and optimal solution and also large training set enough to search the weights of the network. SVM extracts the optimal solution with the small training set by capturing geometric characteristics of feature space without deriving weights of networks from the training data. In this study, we show the advantage of SVM approach over BPN to the problem of corporate bankruptcy prediction. SVM shows the highest level of accuracies and better generalization performance than BPN especially when the training set size is smaller.

Gender Difference in Relationship between Health-Related Quality of Life and Work Status

This study investigated the association of employment status with health-related quality of life in adult Koreans, as well as the gender difference in the relationship, using a large, nationally representative sample. Using data from the Korea Health Panel survey, we examined the relationship between quality of life measured by EQ-5D and work status among Korean adults. We also tested whether and how the relationship between quality of life and work status differed by gender. Quality of life among working adults was better than among non-working adults. The gap between the two groups was larger among male than female participants. Further, the gender differential effect was larger in the 41–60-year-old age group than in the 18–40-year-old and 61-or-older groups. Being employed has a positive relation to quality of life among adults. Work status plays a more important role in quality of life for men than for women, especially for the working elderly men than working elderly women.

The effects of uncoated paper on skin moisture and transepidermal water loss in bedridden patients

AIMS AND OBJECTIVES The aims of this study were to measure skin moisture and transepidermal water loss after application of uncoated paper and to compare skin moisture and transepidermal water loss after use of uncoated paper and disposable underpads. STUDY DESIGN The study was a cross-over, prospective, open-labeled, randomized trial. SAMPLE AND SETTING Bedridden patients aged≥18 years at a medical center in Korea were included. Treatment order was randomly assigned using block randomization, with a block size of 4 and an assignment rate of one-by-one. METHODS Skin moisture was measured using a Corneometer 825 and transepidermal water loss was measured using a Tewameter 300. RESULTS Skin moisture after application of an uncoated paper was significantly lower than observed after application of a disposable underpad (mean 40.6 and SD 13.1 vs. mean 64.6 and SD 23.7, p<0.001). Transepidermal water loss also showed greater health scores after using uncoated paper (mean 11.1 and SD 5.7 g/m2/hour) than after applying a disposable underpad (mean 23.2 and SD 11.1 g/m2 /hour, p<0.001). There were no statistical between-group differences in room temperature, relative humidity, and body temperature. CONCLUSION We found that uncoated paper was helpful in avoiding excessive moisture without adverse effects. RELEVANCE TO CLINICAL PRACTICE As indicated by the results of this study, uncoated paper can be applied to bed-ridden patients who required incontinence care. Nurses may consider using uncoated paper as one of nursing methods in the routine care of bed-ridden patients for moisture control.

14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer

Purpose 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. Materials and Methods We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. Results Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. Conclusion 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.