👤 Jun Seop Yun

Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling pathways as a multi-functional adapter protein. In particular, the loss of RKIP's function in certain types of cancer cells results in epithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis. In addition, RKIP inhibits autophagy by modulating LC3-lipidation and mTORC1. How the RKIP-dependent inhibition of autophagy is linked to EMT and cancer progression is still under investigation. In this study, we investigated the ways by which RKIP interacts with key gene products in EMT and autophagy during the progression of prostate cancer. We first identified the gene products of interest using the corresponding gene ontology terms. The weighted-gene co-expression network analysis (WGCNA) was applied on a gene expression dataset from three groups of prostate tissues; benign prostate hyperplasia, primary and metastatic cancer. We found two modules of highly co-expressed genes, which were preserved in other independent datasets of prostate cancer tissues. RKIP showed potentially novel interactions with one EMT and seven autophagy gene products (TGFBR1; PIK3C3, PIK3CB, TBC1D25, TBC1D5, TOLLIP, WDR45 and WIPI1). In addition, we identified several upstream transcription modulators that could regulate the expression of these gene products. Finally, we verified some RKIP novel interactions by co-localization using the confocal microscopy analysis in a prostate cancer cell line. To summarize, RKIP interacts with EMT and autophagy as part of the same functional unit in developing prostate cancer. Show less

Both the Wnt/β-catenin and Ras pathways are aberrantly activated in most human colorectal cancers (CRCs) and interact cooperatively in tumor promotion. Inhibition of these signaling may therefore be an ideal strategy for treating CRC. We identified KY1220, a compound that destabilizes both β-catenin and Ras, via targeting the Wnt/β-catenin pathway, and synthesized its derivative KYA1797K. KYA1797K bound directly to the regulators of G-protein signaling domain of axin, initiating β-catenin and Ras degradation through enhancement of the β-catenin destruction complex activating GSK3β. KYA1797K effectively suppressed the growth of CRCs harboring APC and KRAS mutations, as shown by various in vitro studies and by in vivo studies using xenograft and transgenic mouse models of tumors induced by APC and KRAS mutations. Destabilization of both β-catenin and Ras via targeting axin is a potential therapeutic strategy for treatment of CRC and other type cancers activated Wnt/β-catenin and Ras pathways. Show less

Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. We investigated the effects of a Polygoni Multiflori Ramulus extract on melanogenesis and isolated emodin from Polygoni Multiflori as an active compound. In addition, the possible mechanisms of action were examined. We found that emodin inhibited both melanin content and tyrosinase activity concentration and time dependently. Tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 mRNA levels decreased following emodin treatment. However, while the mRNA levels of microphthalmia-associated transcription factor (MITF) were not affected by emodin, emodin reduced MITF protein levels. Furthermore, expression of the liver X-receptor (LXR) α gene, but not the LXR β gene was upregulated by emodin. Moreover, emodin regulated melanogenesis by promoting degradation of the MITF protein by upregulating the LXR α gene. The emodin effects on MITF was found to be mediated by phosphorylation of p42/44 MAPK. Taken together, these findings indicate that the inhibition of melanogenesis by emodin occurs through reduced MITF protein expression, which is mediated by upregulation of the LXR α gene and suggest that emodin may be useful as a hyperpigmentation inhibitor. Show less

Genome-wide association studies have been used extensively to identify genetic variants linked to metabolic syndrome (MetS), but most of them have been conducted in non-Asian populations. This study aimed to evaluate the association between MetS and previously studied single nucleotide polymorphisms (SNPs), and their interaction with health-related behavior in Korean men. Seventeen SNPs were genotyped and their association with MetS and its components was tested in 1193 men who enrolled in the study at Seoul National University Hospital. We found that rs662799 near APOA5 and rs769450 in APOE had significant association with MetS and its components. The SNP rs662799 was associated with increased risk of MetS, elevated triglyceride (TG) and low levels of high-density lipoprotein, while rs769450 was associated with a decreased risk of TG. The SNPs showed interactions between alcohol drinking and physical activity, and TG levels in Korean men. We have identified the genetic association and environmental interaction for MetS in Korean men. These results suggest that a strategy of prevention and treatment should be tailored to personal genotype and the population. Show less

Macrophage foam cell formation by oxidized low-density lipoprotein (oxLDL) is a key step in the progression of atherosclerosis, which is involved in cholesterol influx and efflux in macrophages mediated by related proteins such as peroxisome proliferator-activated receptor γ (PPARγ), CD36, PPARα, liver-X receptor α (LXRα), and ATP-binding cassette transporter A1 (ABCA1). The aim of this study was to investigate the beneficial effects of kimchi methanol extract (KME) and a kimchi active compound, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA) on cholesterol flux in THP-1-derived macrophages treated with oxLDL. The effects of KME and HDMPPA on cell viability and lipid peroxidation were determined. Furthermore, the protein expression of PPARγ, CD36, PPARα, LXRα, and ABCA1 was examined. OxLDL strongly induced cell death and lipid peroxidation in THP-1-derived macrophages. However, KME and HDMPPA significantly improved cell viability and inhibited lipid peroxidation induced by oxLDL in THP-1-derived macrophages (P<.05). Moreover, KME and HDMPPA suppressed CD36 and PPARγ expressions, both of which participate in cholesterol influx. In contrast, KME and HDMPPA augmented LXRα, PPARα, and ABCA1 expression, which are associated with cholesterol efflux. Consequently, KME and HDMPPA suppressed lipid accumulation. These results indicate that KME and HDMPPA may inhibit lipid accumulation, in part, by regulating cholesterol influx- and efflux-related proteins. These findings will thus be useful for future prevention strategies against atherosclerosis. Show less

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder, affecting 6-10% of women of reproductive age. The etiology remains poorly understood. To investigate the differentially expressed proteins from PCOS patients versus healthy women, the protein expression in follicular fluid was analyzed using two-dimensional electrophoresis (2-DE). Since follicular fluid contains a number of secretory proteins required for oocyte fertilization and follicle maturation, it is possible that follicular fluid can be used as a provisional source for identifying pivotal proteins associated with PCOS. In this study, six overexpressed proteins [kininogen 1, cytokeratin 9, antithrombin, fibrinogen γ-chain, apolipoprotein A-IV (apoA-IV) precursor and α-1-B-glycoprotein (A1BG)] in follicular fluids from PCOS patients were identified with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) and nano LC-MS/MS. Western blot analysis confirmed that the protein expression levels of apoA-IV precursor and A1BG were increased in follicular fluid from PCOS patients compared with those from normal controls. The analysis of protein expression for other proteins revealed individual variation. These results facilitate the understanding of the molecular mechanisms of PCOS and provide candidate biomarkers for the development of diagnostic and therapeutic tools. Show less

Human infection by Campylobacter jejuni is mainly through the consumption of contaminated poultry products, which results in gastroenteritis and, rarely, bacteremia and polyneuropathies. In this study, six C. jejuni-specific bacteriophages (CPS1-6) were isolated by the spot-on-the-lawn technique from chicken samples in Korea and characterized for potential use as biocontrol agents. All isolated bacteriophages exhibited a high specificity, being able to lyse only C. jejuni, but not other Gram-negative bacteria, including C. coli, Escherichia coli, Salmonella spp., and Gram-positive bacteria. Bacteriophages contain an icosahedral head and a contractile tail sheath in transmission electron microscopy, and possess ds-DNA with an average genome size of approximately 145 kb; therefore, all bacteriophages are categorized into the Myoviridae family. Bacterial lysis studies in liquid media revealed that CPS2 could be used to control the growth of C. jejuni. Show less

The purpose of this study was to compare low-fat (LF) meal and high-fat (HF) meal on the postprandial lipemic responses according to the -1131T>C polymorphism of the APOA5 gene in a population usually consuming a LF diet and having a high frequency of the variant allele at the APOA5 -1131T>C SNP. This study was conducted using a cross-over design and 49 non-obese healthy men (42.8 +/- 0.7 yrs, 23.9 +/- 0.25 kg/m(2)) participated in the meal tolerance test. They were randomly assigned to consume one of two types of experimental enteral formulae (LF vs HF) with a seven-day interval. Blood samples were collected at 0, 2, 3, 4 and 6h after ingestion and analyzed for total and chylomicron TG, glucose, insulin and free fatty acid. No differences were found in anthropometic parameter, calorie and macronutrient intakes and total energy expenditure between TT (n = 23) and TC + CC (n = 26) men. Fasting total TG were higher in TC + CC men than TT men, but fasting chylomicron TG were not significantly different between TT men and C carriers, TT subjects had no significant differences in postprandial responses of total TG and chylomicron TG and postprandial mean changes of chylomicron TG between LF and HF meal. On the other hand, C carriers had delayed peak time of total TG compared to TT subject and higher postprandial response and mean changes of chylomicron TG at HF meal compared to LF meal. The capacity to clear chylomicron-TG or hydrolyze TG might become a rate-limiting factor on HF diet in TC + CC men resulting in higher postprandial triglyceridemia. Therefore, HF diet for C carriers of the APOA5 gene may be one of important CVD risk factors. Show less

In the yeast, Saccharomyces cerevisiae, cell size is affected by the kind of carbon source in the medium. Here, we present evidence that the Gpr1 receptor and Gpa2 Galpha subunit are required for both maintenance and modulation of cell size in response to glucose. In the presence of glucose, mutants lacking GPR1 or GPA2 gene showed smaller cells than the wild-type strain. Physiological studies revealed that protein synthesis rate was reduced in the mutant strains indicating that reduced growth rate, while the level of mRNAs for CLN1, 2 and 3 was not affected in all strains. Gene chip analysis also revealed a down-regulation in the expression of genes related to biosynthesis of not only protein but also other cellular component in the mutant strains. We also show that GPR1 and GPA2 are required for a rapid increase in cell size in response to glucose. Wild-type cells grown in ethanol quickly increased in size by addition of glucose, while little change was observed in the mutant strains, in which glucose-dependent cell cycle arrest caused by CLN1 repression was somewhat alleviated. Our study indicates that the yeast G-protein coupled receptor system consisting of Gpr1 and Gpa2 regulates cell size by affecting both growth rate and cell division. Show less