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- 저자 : ( Gyung Ah Jung ) (검색결과 31 건)
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Induction of Nanog in neural progenitor cells for adaptive regeneration of ischemic brain
Jung Gyung-Ah,Kim Jin-A,Park Hwan-Woo,Lee Hyemi,Chang Mi-Sook,Cho Kyung-Ok,Song Byeong-Wook,김현준,Kwon Yunhee Kim,Oh Il-Hoan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
NANOG plays a key role in cellular plasticity and the acquisition of the stem cell state during reprogramming, but its role in the regenerative process remains unclear. Here, we show that the induction of NANOG in neuronal cells is necessary for the physiological initiation of neuronal regeneration in response to ischemic stress. Specifically, we found that NANOG was preferentially expressed in undifferentiated neuronal cells, and forced expression of Nanog in neural progenitor cells (NPCs) promoted their self-renewing expansion both in ex-vivo slice cultures and in vitro limiting dilution analysis. Notably, the upstream region of the Nanog gene contains sequence motifs for hypoxia-inducible factor-1 alpha (HIF-1α). Therefore, cerebral neurons exposed to hypoxia significantly upregulated NANOG expression selectively in primitive (CD133+) cells, but not in mature cells, leading to the expansion of NPCs. Notably, up to 80% of the neuronal expansion induced by hypoxia was attributed to NANOG-expressing neuronal cells, whereas knockdown during hypoxia abolished this expansion and was accompanied by the downregulation of other pluripotency-related genes. Moreover, the number of NANOG-expressing neuronal cells were transiently increased in response to ischemic insult, predominantly in the infarct area of brain regions undergoing neurogenesis, but not in non-neurogenic loci. Together, these findings reveal a functional effect of NANOG-induction for the initiation of adaptive neuronal regeneration among heterogeneous NPC subsets, pointing to cellular plasticity as a potential link between regeneration and reprogramming processes.
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Jung, Gyung-Ah,Shin, Bong-Shik,Jang, Yeon-Sue,Sohn, Jae-Bum,Woo, Seon-Rang,Kim, Jung-Eun,Choi, Go,Lee, Kyung-Mi,Min, Bon-Hong,Lee, Kee-Ho,Park, Gil-Hong Korean Society for Biochemistry and Molecular Bion 2011 Experimental and molecular medicine Vol.43 No.10
Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-$p21^{Cip/WAF1}$ activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and $p21^{Cip/WAF1}$ short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.
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Epidermal Growth Factor (EGF)에 의한 GH₃ 종양세포의 성장억제에 관한 연구
정경아(Gyung-Ah Jung),남선영(Seon Young Nam),이병란(Byung-Lan Lee) 대한해부학회 2001 Anatomy & Cell Biology Vol.34 No.3
젖샘자극호르몬(프로락틴, PRL)을 분비하는 뇌하수체 종양에 대한 일반적인 약물 치료제로 도파민 효능약물(agonist)인 bromocriptine이 사용되고 있지만 이에 대해 내성을 보이는 환자가 보고되고 있어 적절한 대책이 필요하다. 성장조절인자인 epidermal growth factor (EGF)는 뇌하수체종양 세포에서 도파민 수용체를 유발시킨다는 보고가 있으나 이와 반대되는 결과도 보고되어 있다. 따라서 본 연구에서는 도파민 수용체의 기능이 없다고 보고되어 있는 GH3 세포배양에 EGF를 투여하여 GH3 세포에서 bromocriptine에 대한 반응에 미치는 EGF 영향을 관찰하였다. 이를 위하여 세포들을 EGF 투여군과 비투여군으로 나누어 EGF의 영향을 관찰하였으며 각 군을 다시 bromocriptine 약물 비투여군 및 투여군으로 나누어서 각 군간의 세포 성장과 아포프토시스 및 PRL 발현상태를 비교하였다. 이때 GH3 세포들을 소태아혈청 (10%)이 포함된 Ham’s F-10 배양액에서 96시간 동안 배양한 후에 약물이 포함된 무혈청 배양액으로 바꾸어 96시간 동안 배양하였다. 그 결과 EGF를 투여한 GH3 세포들에서 세포돌기의 수가 증가하였으나 세포수 및 BrdU 표지율이 유의하게 감소하였는데 아포프토시스의 유의한 변화는 없는 점으로 미루어 보아 EGF는 세포분열을 저해함으로써 세포수를 감소시키는 것으로 사료되었다. 또한 PRL을 발현하는 세포들의 비율이 증가되었으므로 EGF는 GH3 세포를 PRL 세포로 분화시키는 것으로 사료되었다. 그러나 EGF 투여는 bromocriptine에 대한 GH3 세포의 반응에는 영향을 미치지 않는 것으로 관찰되었으므로 도파민 수용체의 기능 증가에는 영향이 없는 것으로 생각되었다. Tamoxifen도 단독투여시에는 아포프토시스를 증가시켜 세포수를 감소시켰으나 bromocriptine과 병용시에는 bromocriptine의 효과를 증가시키지는 않았다. 결론적으로 EGF나tamoxifen 처리가 GH3 세포의 도파민 수용체를 유도시키지는 않는 것으로 사료된다. Some of the pituitary prolactinomas were reported that they don’t have active dopamine receptors and do not respond to bromocriptine which is a dopamine agonist. GH3 cell line which is derived from the rat pituitary tumor cells lacks affinity of dopamine receptors and secrete prolactin as well as small amount of growth hormone. Although it has been reported that epidermal growth factor (EGF) induces functional expression of dopamine receptors on GH3 cells in vitro, there has been a contradictory result. In the present study, EGF effect on the GH3 cell response to the bromocriptine was observed in order to investigate whether EGF induces dopamine receptor expression on dopamine resistant tumors in the absence of serum. GH3 cells were cultured for 4 days in the serum-supplemented medium (SSM) followed by culture in serum-free medium (SFM) with or without EGF. Additionally, effect of tamoxifen was also observed. EGF decreased the cell number and the ratio of cell division of GH3 cells while the ratio of prolactin-immunoreactive cells was increased. However, EGF did not show any significant effect on the GH3 cell response to bromocriptine treatment. Although tamoxifen decreased the GH3 cell number by increasing apoptosis, it did not influence GH3 cell response to bromocriptine. Our results indicate that EGF does not increase the affinity of dopamine receptors on GH3 cells and is not useful for the treatment of the dopamine-resistant prolactinoma.
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Wie, Gyung-Ah,Cho, Yeong-Ah,Kang, Hyun-hee,Ryu, Kyoung-A,Yoo, Min-Kyoung,Kim, Young-A,Jung, Kyu-Won,Kim, Jeongseon,Lee, Joo-Hyuk,Joung, Hyojee Cambridge University Press 2014 The British journal of nutrition Vol.112 No.2
<P>Cancer is a leading cause of death, and the dietary pattern in Korea is changing rapidly from a traditional Korean diet to a Westernised diet. In the present study, we investigated the effects of dietary factors on cancer risk with a prospective cohort study. Among 26 815 individuals who participated in cancer screening examinations from September 2004 to December 2008, 8024 subjects who completed a self-administered questionnaire concerning demographic and lifestyle factors, and a 3 d food record were selected. As of September 2013, 387 cancer cases were identified from the National Cancer Registry System, and the remaining individuals were included in the control group. The hazard ratio (HR) of cancer for the subjects older than or equal to 50 years of age was higher (HR 1·80, 95 % CI 1·41, 2·31; <I>P</I>< 0·0001) than that for the other subjects. Red meat consumption, Na intake and obesity (BMI ≥ 25 kg/m<SUP>2</SUP>) were positively associated with overall cancer incidence in men (HR 1·41, 95 % CI 1·02, 1·94; <I>P</I>= 0·0382), gastric cancer (HR 2·34, 95 % CI 1·06, 5·19; <I>P</I>= 0·0365) and thyroid cancer (HR 1·56, 95 % CI 1·05, 2·31; <I>P</I>= 0·0270), respectively. Participants who had at least three dietary risk factors among the high intakes of red meat and Na, low intakes of vegetables and fruits, and obesity suggested by the World Cancer Research Fund/American Institute for Cancer Research at baseline tended to have a higher risk of cancer than the others (HR 1·26, 95 % CI 0·99, 1·60; <I>P</I>= 0·0653). In summary, high intakes of red meat and Na were significant risk factors of cancer among Koreans.</P>
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GH₃ 뇌하수체 종양세포의 분화에 미치는 laminin, Matrigel 및 EGF의 영향
정경아(Gyung-Ah Jung),남선영(Seon Young Nam),이병란(Byung-Lan Lee) 대한해부학회 2001 Anatomy & Cell Biology Vol.34 No.3
뇌하수체 앞엽에는 여러 가지 종류의 호르몬 분비세포가 존재하므로 한가지 종류의 호르몬 세포만을 상대로 연구를 진행하기에 어려움이 있다. GH3 세포는 뇌하수체종양세포로서 젖샘자극호르몬 (PRL)과 성장호르몬을 분비하는 뇌하수체 세포의 특성을 유지하지만 배양기질에 부착력이 낮으며 작은 비율의 세포만이 PRL을 발현하고 장기간 배양시에는 세포의 과증식이 일어나므로 장기배양이 어렵다. 세포사이물질(ECM)은 단세포배양시에 일어나는 세포의 특성소실을 방지하기 위하여 배양기질로 사용되고 있다. ECM과 성장조절인자는 서로 상호작용을 통하여 세포에 영향을 미치나 이때 성장조절인자가 세포에 미치는 영향은 배양기질로 사용된 물질의 종류에 따라 다르다고 알려져 있다. 따라서 본 연구에서는 성장조절인자인 EGF와 세포사이물질을 이용하여 GH3 세포의 PRL 세포로서의 분화를 최대화하고자 하였다. 이를 위하여 세포들의 성장, 증식 및 PRL 발현세포의 빈도를 관찰하기 위하여 세포수측정, bromodeoxyuridine (BrdU) 표지, BrdU 및 PRL에 대한 면역세포화학 염색을 시행하였다. 본 연구의 결과로부터 EGF는 본 연구에 사용된 배양기질인 배양용 플라스틱, laminin 및 Matrigel 위에서 GH3 세포수를 감소시키고 PRL 세포로의 분화를 증가시킴을 알 수 있었고 특히 Matrigel과 함께 사용시 가장 높은 분화도를 나타냄이 관찰되었다. 따라서 GH3 세포의 장기배양시에 과증식을 막고 특성소실을 최소화 하기 위해서는 Matrigel 위의 배양에서 EGF를 투여하는 것이 가장 효과적인 방법으로 사료되었다. This study was performed in order to establish the culture system optimal for the study on pituitary prolactin cells using growth factor and extra cellular matrix components as the culture substrate. The effect of epidermal growth factor (EGF) alone or along with extracellular marix components on GH3 cell growth and PRL expression was assessed using cell count, BrdU-immunocytochemistry and PRL-immunocytochemistry in in vitro cultures on plastic, laminin and Matrigel. EGF decreased the cell growth, BrdU-labeling and increased the PRL-immunoreactive cells regardless of the culture substrate by day 3 of the culture. Matrigel was the best culture substrate to decrease the cell growth and to increase the PRL expression. EGF treatment in the Matrigel culture showed about 80.5% of PRL-immunoreactive cells by day 6 of the culture. These results indicated that Matrigel is the better culture substrate than plastic or laminin to inhibit the overgrowth and to increase the prolactin expression of the GH3 cell and that EGF and Matrigel causes very effective culture environment for the long-term culture of the GH3 cell by synergistic mechanism.
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