Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygen-glucose deprivation.

Chung, Hyunju,Kim, Eunhee,Lee, Dae Hee,Seo, Sanghee,Ju, Sunghee,Lee, Dahm,Kim, Hocheol,Park, Seungjoon Association for the Study of Internal Secretions 2007 Endocrinology Vol.148 No.1

<P>Ghrelin is an endogenous ligand for the GH secretagogue receptor, produced and secreted mainly from the stomach. Ghrelin stimulates GH release and induces positive energy balances. Previous studies have reported that ghrelin inhibits apoptosis in several cell types, but its antiapoptotic effect in neuronal cells is unknown. Therefore, we investigated the role of ghrelin in ischemic neuronal injury using primary hypothalamic neurons exposed to oxygen-glucose deprivation (OGD). Here we report that treatment of hypothalamic neurons with ghrelin inhibited OGD-induced cell death and apoptosis. Exposure of neurons to ghrelin caused rapid activation of ERK1/2. Ghrelin-induced activation of ERK1/2 and the antiapoptotic effect of ghrelin were blocked by chemical inhibition of MAPK, phosphatidylinositol 3 kinase, protein kinase C, and protein kinase A. Ghrelin attenuated OGD-induced activation of c-Jun NH2-terminal kinase and p-38 but not ERK1/2. We also investigated ghrelin regulation of apoptosis at the mitochondrial level. Ghrelin protected cells from OGD insult by inhibiting reactive oxygen species generation and stabilizing mitochondrial transmembrane potential. In addition, ghrelin-treated cells showed an increased Bcl-2/Bax ratio, prevention of cytochrome c release, and inhibition of caspase-3 activation. Finally, in vivo administration of ghrelin significantly reduced infarct volume in an animal model of ischemia. Our data indicate that ghrelin may act as a survival factor that preserves mitochondrial integrity and inhibits apoptotic pathways.</P>

Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells

Chung, Hyunju,Li, Endan,Kim, Yumi,Kim, Sehee,Park, Seungjoon Society for Endocrinology 2013 The Journal of endocrinology Vol.218 No.1

<P>Ghrelin, an endogenous ligand for the GH secretagogue receptor (GHS-R) receptor 1a (GHS-R1a), has been implicated in several physiologic processes involving the hippocampus. The aim of this study was to investigate the molecular mechanisms of ghrelin-stimulated neurogenesis using cultured adult rat hippocampal neural stem cells (NSCs). The expression of GHS-R1a was detected in hippocampal NSCs, as assessed by western blot analysis and immunocytochemistry. Ghrelin treatment increased the proliferation of cultured hippocampal NSCs assessed by BrdU incorporation. The exposure of cells to the receptor-specific antagonist <SMALL>d</SMALL>-Lys-3-GHRP-6 abolished the proliferative effect of ghrelin. By contrast, ghrelin showed no significant effect on cell differentiation. The expression of GHS-R1a was significantly increased by ghrelin treatment. The analysis of signaling pathways showed that ghrelin caused rapid activation of ERK1/2 and Akt, which were blocked by the GHS-R1a antagonist. In addition, ghrelin stimulated the phosphorylation of Akt downstream effectors, such as glycogen synthase kinase (GSK)-3β, mammalian target of rapamycin (mTOR), and p70<SUP>S6K</SUP>. The activation of STAT3 was also caused by ghrelin treatment. Furthermore, pretreatment of cells with specific inhibitors of MEK/ERK1/2, phosphatidylinositol-3-kinase (PI3K)/Akt, mTOR, and Jak2/STAT3 attenuated ghrelin-induced cell proliferation. Taken together, our results support a role for ghrelin in adult hippocampal neurogenesis and suggest the involvement of the ERK1/2, PI3K/Akt, and STAT3 signaling pathways in the mediation of the actions of ghrelin on neurogenesis. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β and activation of mTOR/p70<SUP>S6K</SUP> contribute to the proliferative effect of ghrelin.</P>

Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation

Chung, Hyunju,Choi, Junghyun,Park, Seungjoon The Japan Endocrine Society 2018 Endocrine journal Vol.65 No.1

Ghrelin regulates cell cycle-related gene expression in cultured hippocampal neural stem cells

Chung, Hyunju,Park, Seungjoon Society for Endocrinology 2016 The Journal of endocrinology Vol.230 No.2

<P>We have previously demonstrated that ghrelin stimulates the cellular proliferation of cultured adult rat hippocampal neural stem cells (NSCs). However, little is known about the molecular mechanisms by which ghrelin regulates cell cycle progression. The purpose of this study was to investigate the potential effects of ghrelin on cell cycle regulatory molecules in cultured hippocampal NSCs. Ghrelin treatment increased proliferation assessed by CCK-8 proliferation assay. The expression levels of proliferating cell nuclear antigen and cell division control 2, well-known cell-proliferating markers, were also increased by ghrelin. Fluorescence-activated cell sorting analysis revealed that ghrelin promoted progression of cell cycle from G(0)/G(1) to S phase, whereas this progression was attenuated by the pretreatment with specific inhibitors of MEK/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/Akt, mammalian target of rapamycin, and janus kinase 2/signal transducer and activator of transcription 3. Ghrelin-induced proliferative effect was associated with increased expression of E2F1 transcription factor in the nucleus, as determined by Western blotting and immunofluorescence. We also found that ghrelin caused an increase in protein levels of positive regulators of cell cycle, such as cyclin A and cyclin-dependent kinase (CDK) 2. Moreover, p27(KIP1) and p57(KIP2) protein levels were reduced when cell were exposed to ghrelin, suggesting downregulation of CDK inhibitors may contribute to proliferative effect of ghrelin. Our data suggest that ghrelin targets both cell cycle positive and negative regulators to stimulate proliferation of cultured hippocampal NSCs.</P>

Ghrelin suppresses tunicamycin- or thapsigargin-triggered endoplasmic reticulum stress-mediated apoptosis in primary cultured rat cortical neuronal cells

Chung, Hyunju,Chung, Ho-Yeon,Bae, Chong Woo,Kim, Chong-Jin,Park, Seungjoon The Japan Endocrine Society 2011 Endocrine journal Vol.58 No.5

<P>Ghrelin functions as a neuroprotective agent and rescues neurons from various insults. However, the molecular mechanisms underlying ghrelin neuroprotection remains to be elucidated. An accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then induces ER stress-mediated cell death. Here, we report that acylated ghrelin inhibited tunicamycin- or thapsigargin-triggered ER stress-induced apoptotic cell death in primary rat cortical neurons. An analysis using a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), LY294002, showed that ghrelin prevented apoptosis via the activation of PI3K signaling pathway. Ghrelin suppressed tunicamycin- or thapsigargin-induced upregulation and nuclear translocation of C/EBP homologous protein (CHOP). Ghrelin also inhibited tunicamycin or thapsigargin induction of PRK-like ER kinase (PERK), eukaryotic translation initiation factor-2α (eIF2α) and activating transcription factor (ATF) 4. Exposure of cells to tunicamycin or thapsigargin resulted in nuclear translocation of forkhead box protein O1 (Foxo1), which was reduced by pretreatment with ghrelin. The protective effect of ghrelin was accompanied by an increased phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. Furthermore, ghrelin phosphorylated and inactivated pro-apoptotic BAD and Foxo1. In addition, phospho-Akt was translocated to the nucleus in response to ghrelin and PI3K inhibition by LY294002 prevented ghrelin-induced effect on phospho-Akt localization. Our study suggests that suppression of CHOP activation via the inhibition of PERK/eIF2α/ATF4 pathway and prevention of Foxo1 activation and nuclear translocation may contribute to ghrelin-mediated neuroprotection during ER stress responses. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β, BAD and Foxo1 may be associated with the anti-apoptotic effect of ghrelin.</P>

IGF-I inhibition of apoptosis is associated with decreased expression of prostate apoptosis response-4.

Chung, Hyunju,Seo, Sanghee,Moon, Minho,Park, Seungjoon Journal of Endocrinology, Ltd. [etc.] 2007 The Journal of endocrinology Vol.194 No.1

<P>The neuronal damage caused by ischemic brain injury is associated with increased apoptosis. IGF-I exposure promotes neuronal defense and survival against ischemic insult by inhibiting apoptotic processes. We investigated the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the expression of which is increased after ischemic injury, in IGF-I-mediated inhibition of apoptosis using PC12 cells exposed to oxygen-glucose deprivation (OGD). The OGD insult resulted in significant increases in apoptotic cell death and Par-4 expression, which were prevented by the treatment of cells with an antisense oligonucleotide of Par-4. IGF-I treatment prior to OGD insult significantly reduced the number of apoptotic cells and the OGD-induced increase in Par-4 expression. OGD-induced nuclear translocation of Par-4 was also attenuated by IGF-I treatment. In addition, we demonstrated that the anti-apoptotic effect of IGF-I was blocked by chemical inhibition of a mitogen activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), or protein kinase A (PKA), but not by a protein kinase C inhibitor. Finally, pretreatment of cells with a MAPK or PI3K inhibitor attenuated IGF-I-induced inhibition of Par-4 expression, suggesting that the MAPK and PI3K pathways contribute to IGF-I-induced Par-4 suppression. In contrast, a PKA inhibitor failed to alter the inhibitory effect of IGF-I on Par-4. These findings indicate that in PC12 cells exposed to OGD insult, IGF-I protects cells from apoptosis, at least in part through the inhibition of Par-4 expression.</P>

Effects of implant alignment and load direction on mandibular bone and implant: finite element analysis

Hyunju Chung(정현주),Chan Park(박찬),Kwi-Dug Yun(윤귀덕),Hyun-Pil Lim(임현필),Sang-Won Park(박상원),Hongso Yang(양홍서) 대한턱관절교합학회 2020 구강회복응용과학지 Vol.36 No.3

Vowel Formant Trajectory Patterns for Shared Vowels of American English and Korean

Chung Hyunju,Kong Eun Jong,Weismer Gary 한국음성학회 2010 말소리와 음성과학 Vol.2 No.4

The purpose of this study was to explore the cross-linguistic difference in the spectral movement pattern of American English and Korean vowels. Eight American vowels /?/, /e/, /?/, /i/, /?/, /o/, /u/, and /?/, and five Korean vowels, /a/, /e/, /i/, /o/ and /u/ in a fricative-vowel environment produced by adult speakers of each language were analyzed. The spectral movement patterns of the first two formant frequency values were measured and analyzed. The results showed that Korean vowels had minimal spectral movement, both in F1 and F2 values, as compared to American English vowels. Moreover, no consistent direction of movement was found in the three corner Korean vowels, while American English vowels showed consistent direction of movement for each vowel of the same phonemic category.

내측 연결 및 외측 연결 방식으로 설계된 임플란트의 3차원적 유한요소 응력 분석

정현주(Hyunju Chung),양성표(Sung-Pyo Yang),박재호(Jae-Ho Park),박찬(Chan Park),신진호(Jin-Ho Shin),양홍서(Hongso Yang) 대한턱관절교합학회 2017 구강회복응용과학지 Vol.33 No.3

정신장애인의 ‘더빙 프로젝트’ 참여경험에 관한 연구 : “나의 목소리를 찾아서”

정현주(HyunJu Chung),이은주(EunJoo Lee) 서울사이버대학교 미래사회전략연구소 2021 미래사회 Vol.12 No.1

본 연구는 정신장애인의 회복활동을 지원하고 세상과 소통할 수 있도록 지원하는 인식개선사업 더빙프로젝트 에서 정신장애인들이 어떤 경험과 변화를 겪고 있는지 이들의 시각과 언어를 통해 이해하고, 그 과정과 맥락을 구체적으로 드러내고자 하였다. 이를 위해 총 10명의 연구참여자를 대상으로 일반적 질적연구를 활용하여 연구한 결과, 당사자들은 더빙 프로젝트 참여경험의 의미를 나의 꿈을 찾아가는 회복여행 이라고 인식하고 있었으며, 사회적 편견에 대항하여 적극적으로 자기 목소리를 내는 과정을 통해 긍정적 자아인식과 자존감의 향상, 참여자간 연대감의 증진을 이루어가고 있었다. 이러한 본 연구결과는 정신장애인 인식개선 사업 참여경험이 당사자들에게 긍정적이고 가치있는 사회적 역할을 보장함으로써 이들의 삶속에서 미래를 향한 회복을 만들어 가는데 유용함을 증명하고 있다. The purpose of this research is to understand the experience and change of people with mental health problems participating in a two and half-year improved program of mental disability awareness, ‘Dubbing Project’ through their view and language, and to explore the detailed processes and contexts of their experience. A total of 10 people with mental health problems participated in this qualitative research. The results showed that participants described the experience of the project as a main theme of ‘a recovery journey to search for my dream’ and achieved positive self-esteem, enhancement of self-respect, and increased connectedness among participants through the process of actively making their voices against social stigma. Therefore, it is found that their experience of participation in ‘Dubbing Project’ was the recovery process toward the future in their life, enabling them to identify positive and valuable social roles.