Jeong-Hyeon Kim

ERK mediates anti-apoptotic effect through phosphorylation and cytoplasmic localization of p21Waf1/Cip1/Sdi in response to DNA damage in normal human embryonic fibroblast (HEF) cells.

Since anti-apoptotic effect of ERK has not been elucidated clearly in DNA-damage-induced cell death, the role of ERK was examined in normal HEF cells treated with mild DNA damage using etoposide or camptothecin. ERK was activated by DNA damage in HEF cells. PD98059 increased apoptosis and reduced DNA-damage-induced p21Waf1/Cip1/Sdi level. Depletion of p21Waf1/Cip1/Sdi induced cell death and PD98059 induced additional cell death. DNA-damage-induced increase in cytoplasmic localization and phosphorylation of threonine residues of p21Waf1/Cip1/Sdi was reversed by PD98059. Thus, the results suggest that ERK pathway mediates anti-apoptotic effects through phosphorylation and cytoplasmic localization of p21Waf1/Cip1/Sdi in response to mild DNA damage.

Nitric Oxide Is an Essential Mediator for Neuronal Differentiation of Rat Primary Cortical Neuron Cells

Nitric oxide (NO) regulates proliferation, differentiation and survival of neurons. Although NO is reported to involve in NGF-induced differentiation of PC12 cells, the role of NO has not been characterized in primary neuron cells. Therefore, we investigated the role of NO in neuronal differentiation of primary cortical neuron cells. Primary cortical neuron cells were prepared from rat embryos of embryonic day 18 and treated with NMMA (NOS inhibitor) or PTIO (NO scavenger). Neurite outgrowth of neuron cells was counted and the mRNA levels of p21, p27, c-jun and c-myc were measured by RT-PCR. Neurite outgrowth of primary cortical neuron cells was inhibited a little by NOS inhibitor and completely by NO scavenger. The mRNA levels of p21 and p27, differentiation-induced growth arrest genes were increased during differentiation, but they were decreased by NOS inhibitor or NO scavenger. On the other hand, the level of c-jun mRNA was not changed and the level of c-myc mRNA was increased during differentiation differently from previously reported. The levels of these mRNA were reversed in NOS inhibitor- or NO scavenger-treated cells. The level of nNOS protein was not changed but NOS activity was inhibited largely by NOS inhibitor or NO scavenger. These results suggest that NO is an essential mediator for neuronal differentiation of primary cortical neuron cells.

Calorie restriction (CR) reduces age-dependent decline of non-homologous end joining (NHEJ) activity in rat tissues

Even though CR has shown to enhance base excision repair (BER) and nucleotide excision repair (NER) capacities, it has not been reported whether CR can enhance non-homologous end joining (NHEJ) activity. To examine the effect of CR on NHEJ activity, ad libitum (AL)- and calorie restricted (CR)-dieted rats were used. Age-dependent decline of NHEJ activity was apparent in the lung, liver, and kidney and appeared to be slightly decreased in spleen. CR reduced age-dependent decline of NHEJ activity in all tissues, even though the extent of recovery was variable among tissues. Moreover, CR appeared to reduce age-dependent decline of XRCC4 protein level. These results suggest that CR could reduce age-dependent decline of NHEJ activity in various tissues of rats possibly through up-regulation of XRCC4.

The relationship between suicidal behaviors and atopic dermatitis in Korean adolescents

Atopic dermatitis is a common skin disease in adolescents, which may have a negative effect on the mental and emotional health. We investigated the relationship between atopic dermatitis and suicidal behaviors in Korean adolescents. Participants included 74,186 adolescents (38,221 boys and 35,965 girls) in middle and high school who completed the Eighth Korea Youth Risk Behavior Web-Based Survey. There were significant associations between atopic dermatitis and suicidal behaviors for girls. The overestimation of weight perception might have an additive impact on suicidal risk among girls. However, there were no significant associations between atopic dermatitis and suicidal behaviors in boys.

Butyrate-induced differentiation of PC12 cells to chromaffin cells involves cell adhesion and induction of extracellular proteins and cell adhesion proteins

Abstract PC12 cells were differentiated into the cells of chromaffin phenotype by butyrate treatment. Cells were aggregated and formed tight cell adhesion. To investigate the molecular change in this differentiation, we examined expression levels of cell adhesion proteins and extracellular proteins during butyrate induced-differentiation of PC12 cells. Integrin β1, integrin α7, E cadherin, VCAM, collagen-I, fibronectin, desmoglein and connexin were increased during differentiation. The levels of clusterin and secreted clusterin were also increased. These increased levels of cell adhesion proteins and extracellular proteins appear to induce cell aggregation and tight cell adhesion. The levels of p21, p27 and p16 were increased probably because of differentiation-related growth arrest during differentiation. Prolonged incubation of butyrate up to 1 day was required for differentiation. Signal transduction pathways for this differentiatiom could not be identified since various inhibitors had no effect. The results showed that butyrate-induced differentiation of PC12 cells to chromaffin cells involves tight cell adhesion and induction of extracellular proteins and cell adhesion proteins.

FOXO3a Activation by oxyresveratrol of Morus bombycis koidzumi extract mediates antioxidant activity

ABSTRACT Although Morus bombycis koidzumi (MB) extract has been reported to have antioxidant activity, the mechanism underlying its antioxidant activity has not been elucidated. In this report, we showed that FOXO3a was activated by MB extract. FOXO3a is a transcription factor that is involved in various biological functions such as cell cycle control, apoptosis, DNA repair, and reactive oxygen species (ROS) detoxification. Protein levels of FOXO3a and MnSOD, target gene of FOXO3a were increased by the MB extract. The ROS level was decreased by the MB extract in human embryonic fibroblast (HEF) cells. Among components of the MB extract, oxyresveratrol (2′,4′,3,5-tetrahydroxystilbene) was identified and turned out to activate FOXO3a. The protein level of FOXO3a was increased by oxyresveratrol. Promoter activities of target genes of FOXO3a such as MnSOD, p27, and GADD45 were activated by oxyresveratrol. The ROS level was decreased by oxyresveratrol in HEF cells in a dose-dependent manner. However, the ROS level was elevated in HEF cells when FOXO3a was knocked down by si-FOXO3a, while overexpression of wt-FOXO3a decreased the cellular ROS level, indicating that antioxidant activity by oxyresveratrol is FOXO3a-dependent. These results indicate that oxyresveratrol of MB extract mediates an antioxidant activity through upregulation of MnSOD by FOXO3a activation.

Abstract 3520: Solidago virga-aurea extract induced apoptosis of breast cancer cells through FOXO3 mediated bim expression

Solidago virga-aurea (European goldenrod or woundwort) is an herbaceous perennial plant of the family Asteraceae. It is used for medical system with astringent, diuretic, antiseptic and homeopathic properties. And the studies about Solidago virga-aurea are in progress for the other functions. Recently, we found that Solidago virga-aurea extract induces apoptosis of breast cancer cells. MTT assay showed that cellular viability was decreased in Solidago virga-aurea extract treated MDA-MB-231 and MCF-7 breast cancer cell lines by dose and time dependent manner. And apoptotic protein, especially bim, was increased in Solidago virga-aurea extract treated MCF-7 cell line. However, anti-apoptotic protein, Bcl-xL, does not changed by Solidago virga-aurea extract. In order to find out positive regulator of bim expression, we tested whether FOXO (forkhead-box transcription factor, group O) 3a and AMPK (5’ AMP-activated protein kinase) protein expression. In immunoblot analysis showed that FOXO3a expression level was dramatically increased in Solidago virga-aurea treated MCF-7 cells without changes of AMPK expression. Moreover, immunostaining showed that Solidago virga-aurea induces co-localization of FOXO3a and bim proteins in MCF-7 and MB-231 cells. Taken together, Solidago virga-aurea induces apoptosis by FOXO3a mediated up-regulation of bim protein. The mechanisms of Solidago virga-aurea mediated FOXO3a regulation is not fully elucidated yet, but further studies about this molecular mechanism between two proteins will give some ideas for cancer therapies for certain breast cancer patients. Citation Format: Haesung Kim, Chea Ha Kim, Jeong-Hyeon Kim, Jeong-Min Lee, Jeong-Ho Jeon, Jae-Yong Lee. Solidago virga-aurea extract induced apoptosis of breast cancer cells through FOXO3 mediated bim expression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3520.

Coffee consumption and coronary heart disease risk as estimated using the Framingham risk score

BACKGROUND AND OBJECTIVES Although concerns regarding the influence of coffee consumption on human health have accompanied the massive increase in coffee consumption, the effects of coffee intake on the risk for coronary heart disease (CHD) remain controversial. Therefore, we evaluated the association between coffee consumption and CHD risk as estimated using the Framingham risk model in Korean adults. METHODS AND STUDY DESIGN This cross-sectional study involved 3,987 participants aged 30-74 years who participated in the fifth Korea National Health and Nutrition Examination Survey conducted in 2010. The frequency of coffee consumption was self-reported and classified into 4 categories (non-drinker, 1, 2, and >=3 cups/day). The 10-year risk for CHD was determined from the Framingham risk score. RESULTS Across the levels of coffee consumption, there were significant differences in the frequency of smoking among men and advanced age, low high-density lipoprotein cholesterol level, diabetes, and smoking among women. In the multiple logistic regression analyses, the adjusted odds ratios (95% CI) for >=20% 10-year CHD risk was 0.211 (0.060-0.745) for women who consumed >=3 cups of coffee per day compared with women who consumed <1 cup per day. For women, a significant dose-response inverse association between the level of coffee consumption and 10-year CHD risk persisted even after adjusting for multiple confounding factors. For the men, however, there was no significant association between coffee consumption and 10-year CHD risk. CONCLUSIONS Coffee consumption is associated with a lower risk for CHD in Korean women.