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Leucine Zipper as a Fine Tuner for the DNA Binding; Revisited with Molecular Dynamics Simulation of the Fos-Jun bZIP Complex

  • 최용훈;양철학;김현원;정선호
    • Bulletin of the Korean Chemical Society
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    • v.20 no.11
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    • pp.1319-1322
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    • 1999
  • Leucine zipper dynamically tunes the degree of bifurcation of the DNA binding segments in the basic region of the Fos-Jun bZIP complex. Molecular dynamics simulation indicated that site-specific mutagenesis of conserved leucine residues inside the leucine zipper domain caused the change of dynamic behavior of the basic region, and efficient DNA binding occurs only within a certain range of distance between the two DNA binding segments in the basic region. Distribution of α-helices in the hinge region is also suggested to influence the bifurcation of the DNA binding segments.

Fatty Acid Composition and Sensory Characteristics of Eggs Obtained from Hens Fed Flaxseed Oil, Dried Whitebait and/or Fructo-oligosaccharide

  • Yi, Haechang;Hwang, Keum Taek;Regenstein, Joe M.;Shin, Sung Woo
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.7
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    • pp.1026-1034
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    • 2014
  • This study was conducted to assess the effects of flaxseed oil and dried whitebait as a source of ${\omega}$-3 fatty acids (${\omega}$-3 FA), which could be used to produce eggs enriched with ${\omega}$-3 FA, and of fructo-oligosaccharide (FOS) as a source of prebiotics on performance of hens (commercial Hy-Line Brown laying hens), and FA composition, internal quality, and sensory characteristics of the eggs. Dietary FOS increased egg weight. The amounts of ${\alpha}$-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) in the eggs from the hens fed the flaxseed oil alone or flaxseed oil+dried whitebait diets were higher than those of the control. Hedonic scores for off-flavor, fishy flavor, buttery taste and overall acceptability of the eggs from the hens fed the diet containing flaxseed oil+dried whitebait were lower (p<0.05) than those of the control. Overall acceptability of the eggs from the hens fed the diet containing soybean oil+dried whitebait was lower (p<0.05) than that of the control. However, all the sensory attributes of the eggs from the hens fed the diet containing flaxseed oil, dried whitebait and FOS were not significantly different from those of the control. These results confirmed that flaxseed oil increases the ALA content in the eggs and a combination of flaxseed oil and dried whitebait increases EPA and DHA in the eggs. Of significance was that addition of FOS to the flaxseed oil+dried whitebait diet improves the sensory characteristics of the eggs enriched with ${\omega}$-3 FA.

Effects of Sophorae Radix Extract in Rat Cardiac Endothelial Cells (고삼 추출물이 배양 심장내피세포에 미치는 영향)

  • Kwon Kang Beom;Park Cheon Su;Kim In Gyu;Kim Hyun Gyu;Choi Ki Bang;Kim Yong Bok;Ryu Do Gon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.220-224
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    • 2003
  • To test the protective effect of Sophorae Radix (SR) on the damage of cardiac endothelial cells by xanthine oxidase (XO)/hypoxanthine (HX)-induced oxygen tree radical, Neutral Red (NR), lactate dyhydrogenase (LDH), and c-fos immunopositive cells assay were used in the presence of SR extract. The results of these experiments were obtained as follows ; Cardiac endothelial cells treated with XO/HX showed the cytotoxicity such as a decrease in viability, and increases in LDH activity and c-fos immunopositive cells. Cardiac endothelial cells pretreated with SR extract protected the increase of LDH activity. Alos, cardiac endothelial cells pretreated with SR extract inhibited the increase of c-fos immunopositive cells. These results show that XO/HX induces toxic effects in cultured cardiac endothelial cells derived from neonatal rat, and suggest that SR extract is very effective in the prevention of XO/HX-induced toxicity.

The Effect of Acupuncture on Methamphetamineinduced Locomotor Activity and C-Fos Expression in Rat Brain (흰쥐의 급성 메스암페타민 투여에 대한 침(鍼)의 효과)

  • Choi, Seong-Hun;Lee, Bong-Hyo;Park, In-Sick;Choi, Nan-Hee;Kim, Kwang-Joong;Jang, Eun-Young;Ku, Sae-Kwang;Song, Ick-Soo;Yang, Chae-Ha
    • Journal of Acupuncture Research
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    • v.26 no.1
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    • pp.39-47
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    • 2009
  • Objectives : The mesolimbic dopamine system is believed to play a major role in the reinforcing effect and behavioral hyperactivity of abused drugs including methamphetamine. In the present study, the effect of acupuncture on methamphetamine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens of rats were examined. Methods : Male Sprague-Dawley rats received acupuncture at bilateral Yanggu($SI_5$) point for 30seconds immediately before the subcutaneous injection of saline or methamphetamine(0.5mg/kg). The total amount of locomotor activity for 90min were measured just before brain samples were taken for immunohistochemistry. Results : Results showed that acupuncture at the specific point $SI_5$, but not control point(Kunlun, $BL_{60}$) significantly reduced locomotor activity and c-Fos expression in the striatum and nucleus accumbens induced by acute administration of methamphetamine. Conclusions : These results suggest that acupuncture may be effective in suppressing the reinforcing effect of methamphetamine by regulating neuronal activity.

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EFFECT OF CYCLOHEXIMIDE ON KAINIC ACID-INDUCED PROENKEPHALIN mRNA INCREASE IN THE RAT HIPPOCAMPUS: ROLE OF PROTO-ONCOGENES

  • Je-Seong. Won;Suh, Hong-Won;Song, Dong-Keun;Kim, Yung-Hi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.180-180
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    • 1996
  • Previous studies have shown that kainic acid (KA) causes an elevation of hippocampal proenkephalin mRNA level. However, the role of proto-oncogene products, such as c-Fos, c-Jun and Fra proteins in the regulation of KA-induced proenkephalin mRNA increase in the hippocampus has not been well characterized. Thus, in the present study, the effect of cycloheximide (CHX) on KA-induced proenkephalin mRNA and immediate early gene products induction was examined. After pretreating with either vehicle or CHX (20 mg/kg, s.c.) for 30 min, KA (10 mg/kg) was administered s.c. The animals were sacrificed 1,2, or 8 hrs after KA administration. Total RNA and were isolated for Northern blot assay, and proteins were isolated for Western and electrophoretic gel-shift assays. First, we found that CHX inhibited KA-induced proenkephalin mRNA increase without altering intracellular proenkephalin protein level. Secondly, Western blot assays showed that KA increased c-Fos, c-Jun and Fra proteins at 1,2, and 8 hrs and CHX inhibited these immediate early gene products. Finally, electrophoretic gel shift assays revealed that KA increased both AP-1 and ENKCRE-2 DNA binding activities. Furthermore, CHX attenuated KA-induced AP-1 and ENKCRE-2 DNA binding activities. Both AP-1 and ENKCRE-2 DNA binding activities were abolished by cold AP-1 or ENKCRE-2 oligonucleotides, and further reduced by antibodies against c-Fos or c-Jun. Antibody against CREB reduced ENKCRE-2, but not AP-1, DNA binding activity. Our results suggest that on-going protein synthesis is required for elevation of hippocampal proenkephalin mRNA level induced by KA. All c-Fos, c-Jun, and Fra proteins appears to be involved in the regulation of hippocampal proenkephalin mRNA level induced by KA (This study was supported by a grant from KOSEF).

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Effect of Chengsimyeunja-eum (淸心蓮子飮) and Sunghyangjungi-san (星香正氣散) on Streptozotocin-induced Ischemic Damaged Diabetic Rats (청심연자음(淸心蓮子飮)과 성향정기산(星香正氣散)이 Streptozotocin유발(誘發) 당뇨(糖尿)흰쥐의 뇌허혈 손상(腦虛血 損傷)에 미치는 영향(影響))

  • Park, Soon-Il;Lee, Won-Chul
    • The Journal of Korean Medicine
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    • v.28 no.3 s.71
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    • pp.216-231
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    • 2007
  • Objectives : Chengsimyeunja-eum and Sunghyangjungi-san are prescriptions used for cerebral infarction clinically; it is known that these formulas reduce ischemic damage. According to previous research data, controlling certain types of glucose is considered to decrease the risk of cerebral infarction. Based on this fact, we investigated the effects of Chengsimyeunja-eum and Sunghyangjungi-san extracts on reperfusion following ischemic damage to diabetic rats, the change of c-FOS and Bax positive neurons in the hippocampus and cerebral cortex and protein through immunohistochemical methods, changes of serum glucose level, serum triglyceride level, and hepatic glucokinase activity. Methods : We induced ischemic damaged in diabetic rats, and the rats were administered Chengsimyeunja-eum and Sunghyangjungi-san extracts. Results : Chengsimyeunja-eum demonstrated significant decrease of c-Fos positive neurons in both hippocampus and cerebral cortex as well as a significant decrease of Bax positive neurons in hippocampus after ischemic damage on diabetic rats and decrease of serum glucose level after ischemic damage on diabetic rats. Sunghyangjungi-san demonstrated significant decreases of c-Fos and Bax positive neurons in both hippocampus and cerebral cortex after ischemic damage on diabetic rats. Conclusions : Chengsimyeunja-eum, effect on glucose level control, has a remarkable effect of protection of neurons not effective on glucose level. Sunghyangjungi-san showed neuroprotective effect through preventing neuronal cell death.

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Effects of Rehmanniae Radix on HPA Axis System and Catecholamienrgic System in FST (생지황(生地黃)이 강제수영부하시험에서 HPA Axis System과 Catecholaminergic System에 미치는 영향)

  • Park, Jae-Beom;Lee, Tae-Hee
    • Herbal Formula Science
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    • v.18 no.1
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    • pp.133-144
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    • 2010
  • Object : The effects of Rehmanniae Radix(RR) on HPA Axis system and Catecholaminergic system was investigated. Methods : we performed the Forced Swimming Test(FST). Also the expression of Corticotropin -Releasing Factor(CRF), c-Fos and Tyrosine Hydorxylase(TH) was measured by immunohistochemical method at Paraventricular Nucleus(PVN), Locus Coeruleus(LC) and Ventral Tegmental Area(VTA). Results : 1. The duration of immobility in the Forced Swimming Test was significantly decreased in the Rehmanniae Radix 400 mg/kg groups in comparison with the control group(p<0.05). 2. Comparing to the control group, CRF expression was significantly decreased in the Rehmanniae Radix 400 mg/kg treated group in comparison with the control group(p<0.01). 3. c-Fos expression was significantly decreased at PVN in the Rehmanniae Radix 100 mg/kg treated group in comparison with the control group(p<0.01). 4. TH expression was significantly increased at LC in the Rehmanniae Radix 100 mg/kg and 400 mg/kg treated group in comparison with the control group(p<0.001). 5. TH expression was significantly decreased at VTA in the Rehmanniae Radix 100 mg/kg and 400 mg/kg treated group in comparison with the control group(p<0.001). Conclusion : According to the results, it can be considered that Rehmanniae Radix has antidepressant effect by showing the reduction of immobility in FST through the decreased expression of CRF, c-Fos in PVN and TH in VTA.

Activation of Vestibular Neurons Projecting to Autonomic Brain Stem Nuclei Following Acute Hypotension in Rats

  • Choi, Myoung-Ae;Wang, Won-Ki;Choi, Dong-Ok;Kim, Min-Sun;Park, Byung-Rim
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.3
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    • pp.133-140
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    • 2004
  • The purpose of the present study was to elucidate the possible involvement of the medial vestibular nucleus (MVN) and inferior vestibular nucleus (IVN) following acute hypotension in the vestibuloautonomic reflex through vestibulosolitary or vestibuloventrolateral projections. Acute hypotension-induced cFos expression was assessed in combination with retrograde cholera toxin B subunit (CTb) tract tracing. After injection of CTb into the solitary region, CTb-labeled neurons were located prominently around the lateral borders of the caudal MVN and medial border of the IVN. The superior vestibular nucleus also had a scattered distribution of CTb-labeled neurons. After injection of CTb toxin into the unilateral VLM, the distributions of CTb-labeled neurons in the MVN and IVN were similar to that observed after injection into the solitary region, although there were fewer CTb-labeled neurons. In the caudal MVN, about 38% and 13% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. In the IVN, 14% and 7% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. Therefore, the present study suggests that acute arterial hypotension may result in activation of vestibulosolitary pathways that mediate behavioral and visceral reflexes, and vestibuloventrolateral medullary pathways that indirectly mediate vestibulosympathetic responses.

A novel biomarker of exercise-induced stress in horses (말의 운동 스트레스에 관한 새로운 생물지표)

  • Lee, Seungwoo;Oh, Dayoung;Kim, Myung-Chul;Kim, Yongbaek;Ryu, Doug-Young
    • Korean Journal of Veterinary Research
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    • v.55 no.4
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    • pp.247-252
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    • 2015
  • Exercise is one of the most common stressors in horses. Although various physiological parameters such as cortisol respond to exercise, there is no reliable parameter for the measurement of exercise-induced stress in sport horses. This study was performed to discover a new biomarker with high sensitivity for exercise-induced stress. The expression of fos mRNA was increased more than 10-fold in horse blood samples collected after an hour of exercise, as compared with before the exercise. The plasma cortisol levels were also increased after the exercise, but only by about two-fold. The fos mRNA levels were well-correlated with plasma cortisol concentrations. These findings suggest that fos mRNA expression in blood may be useful for the measurement of exercise-induced stress in horses.

Inhibitory Effects of Yongbu-tang on Osteoclast Differentiation and Bone Resorption (용부탕의 파골세포 분화 억제와 골 흡수 억제효과)

  • Lee, Jeong Ju;Jo, So Hyun;Park, Min Cheol;Jo, Eun Heui
    • Journal of Acupuncture Research
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    • v.32 no.3
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    • pp.27-40
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    • 2015
  • Objectives : This study was performed to evaluate the effects of water extract of Cervi Parvum Cornu(CPC), Aconiti Lateralis Radix Preparata(ALR), and Yongbu-tang(YBT) on suppression of the receptor activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation and bone resorption. Methods : The effects of CPC, ALR, YBT extracts on osteoclast differentiation were determined by culture of bone marrow macrophage(BMM). The mRNA expression levels of the nuclear factor of activated T-cells cytoplasmic 1(NFATc1), c-Fos and tartrate-resistant acid phosphatase(TRAP) in BMMs were analyzed by reverse transcriptase polymerase chain reaction(RT-PCR). Similarly, the protein expression levels of NFATc1, c-Fos, mitogen-activated protein kinase(MAPK)s and ${\beta}$-actin in cell lysates were measured by western blotting. In addition, effects of CPC, ALR and YBT extracts were determined by means of Lipopolysaccharide(LPS)-induced bone-loss with mice. Results : CPC, ALR and YBT extracts showed remarkable inhibition on RANKL-induced osteoclast differentiation without cytotoxicity. CPC and ALR extracts significantly reduced the protein expression level of NFATc1. YBT extract significantly reduced the mRNA expression levels of c-Fos, NFATc1 and the protein expression levels of c-Fos, NFATc1, AKT, p38, c-Jun N-terminal kinase(JNK). Further, YBT extract suppressed degradation of$ I-{\kappa}B$. And ALR extract significantly restored the bone erosion by LPS treatment in mice. Conclusions : YBT extract showed more remarkable inhibition on osteoclast differentiation than CPC and ALR extracts in vitro. ALR extract showed remarkable inhibition on bone resorption in vivo. Thus, YBT extract can be a useful treatment for bone-loss diseases such as osteoporosis.