• Archives of Pharmacal Research
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• 제25권3호
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• pp.370-374
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• 2002

Administration of dopamine agonist, apomorphine (2 mg/kg, s.c.), produces cage climbing behavior in mice that exhibit typical dopaminergic stimulation. The present study investigated the pCREB expression level in several brain regions following apomorphine treatment in order to determine whether the increased the dopaminergic activation produced by apomorphine accompanies the changes in pCREB immunoreactivity. A mouse brain was removed at 0min, 10 min, 30 min, 1 h, 2 h, 7 h, and 24 h after apomorphine treatment. The brain tissue was fixed by an intracardiac perfusion with ice-cold 4％ paraformaldehyde in PBS. Immunohistochemical study was conducted using the ABC-DAB method. The data showed that the immunoreactivity of pCREB increased in the striatum, nucleus-accumbens, piriform cortex and the dentate gyrus of the hippocampus of a mouse brain 30 min after the apomorphine treatment. Increased immunoreactivity began to diminish 2 h after the apomorphine treatment in all the brain regions measured. The time course for the pCREB immunoreactivity was similar to the behavioral response induced by the apomorphine treatment. These results suggest that activation of the dopamine receptor is accompanied by an increase in pCREB expression in the mouse brain.

• 대한약침학회지
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• 제21권1호
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• pp.35-40
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• 2018

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.299-305
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• 2001

Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

• Tuberculosis and Respiratory Diseases
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• 제59권6호
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• pp.631-637
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• 2005

배 경 : 폐를 포함한 인체내 여러 조직에서 상피세포의 분화 및 증식에 중요한 역할을 담당한다고 알려진 Retinoid acid(RA)와 여러 유전자들에서 전사조절인자로 성장관여 유전자들의 활성화에 관여하며 세포증식 및 분화에 매우 중요한 세포내 조절인자인 cAMP response-element binding protein(CREB)의 폐암종에서의 발현정도를 알아보고 조직학적 차이에 따른 발현도를 비교분석하여 발암과정에서의 관여여부와 역할을 파악하고자 하였다. 방 법 : 중앙대학교 의과대학 부속병원에서 최근 10년간 시행한 기관지내시경 및 흉부외과적 적출을 통해 얻어진 폐암종 조직중 파라핀 포매의 보관상태가 양호한 120예(선암종 60예, 편평세포암종 60예)를 연구대상으로 면역조직화학적 염색을 시행하였다. 결 과 : RAR과 CREB 모두 편평세포암종에 비해 선암종에서 발현이 의의있게 높았고(P<0.05) 선암종에서는 조직학적으로 분화도가 좋을수록 높은 발현율을 보였다(P<0.01). 총 120예의 폐암종에서 RAR과 CREB의 발현을 비교하면 65.8%의 동시발현율을 나타냈다(P<0.05) 결 론 : RAR과 CREB은 폐조직에서 점액상피세포의 분화와 상관관계가 있으며 편평세포암종보다는 선암종의 발암과정에서 일부 의미있는 역할을 수행하리라 생각되었다. 또한 RAR과 CREB의 발현부위도 통계적으로 의미 있는 일치양상을 나타내어 이들은 서로 상호작용에 의해 발암과정 중 일부 역할을 수행하리라 생각된다.

• Journal of Gastric Cancer
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• 제8권4호
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• pp.182-188
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• 2008

목적: 인체 내 여러 조직에서 상피세포의 분화 및 증식에 중요한 역할을 담당한다고 알려진 retinoic acid (RA)와 여러 유전자들에서 전사조절인자로 성장관여 유전자들의 활성화에 관여하며 세포증식 및 분화에 매우 중요한 세포내 조절인자인 CREB의 발현정도와 위선암종간의 상호 연관성 및 병리학적 인자들과의 관계를 관찰하였다. 대상 및 방법: 중앙대학교 의과대학 용산병원에서 1998년 1월부터 2007년 12월까지 위절제술을 시행 받고 위선암종으로 진단받은 환자의 위조직표본 중 보존상태가 양호한 파라핀 포매괴 150예를 연구대상으로 조직 표본에서 면역 조직화학적 염색을 통해 관찰하였다. 결과: 1. RAR의 발현은 장형 위선암종(72.2%)에서 미만형 위선암종(40.5%)보다 높게 나타났으며(P<0.01), 림프절 전이가 있는 경우(74.7%)가 림프절 전이가 없는 경우(49.2%)보다 의미 있는 발현양상을 나타냈다(P<0.01). 2. cAMP response element binding protein (CREB)의 발현은 장형 위선암종(69.4%)에서 미만형 위선암종(38.1%)보다 높게 나타났으며(P<0.01), 림프절 전이가 있는 경우(71.1%)가 림프절 전이가 없는 경우(47.8%)보다 높은 발현양상을 나타냈다(P<0.01). 3. 총 150예의 위선암종에서 RAR은 63.3% (95/150), CREB은 60.7%(91/150)에서 발현을 나타냈다(P<0.01). 결론: 이상의 결과로 RAR과 CREB은 조직학적 분화도 및 종양의 전이와 관련이 있고, 이들의 발현이 장형 위선암종에서의 생물학적 악성도에 관한 예후인자로서 관련이 있으나 이들의 발현이 위선암종에 미치는 생물학적 기전에 대한 추가 연구가 필요하다.

• Journal of Acupuncture Research
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• 제21권3호
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• pp.61-81
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• 2004

Background and Objective : The aim of this study was to investigate the effects of acupuncture and electroacupuncture on the DCX, PSA-NCAM, and pCREB expression in the brain of spontaneously hypertensive rats(SHR). Materials and Methods : SHR were divided into five groups: control group, acupuncture group, 2Hz electroacupuncture(EA) group and 100Hz EA group. We evaluated the changes of the DCX, PSA-NCAM, and pCREB positive cells using immunohistochemical method. In the olfactory bulb, we investigate the optical densities of the immunoactive cells. In the dentate gyrus and the piriform cortex, we count the immunoactive cells under the $100{\times}$ visual field optical microscope. Results : 1. The optical densities of DCX-positive cells in the subependymal zone were significantly decreased in all groups, compared to the control group. 2. The counts of DCX-positive cells in the dentate gyrus were significantly increased in all groups, compared to the control group. The counts of DCX-positive cells in the piriform cortex were significantly increased in the acupuncture and 100Hz EA group, compared to the control group. 3. The optical densities of PSA-NCAM-positive cells in the subependymal zone were significantly decreased in the acupuncture and 2Hz EA group, compared to the control group. 4. The counts of PSA-NCAM-positive cells in the dentate gyrus and the piriform cortex were significantly increased in all group, compared to the control group. 5. The counts of pCREB-positive cells in the dentate gyrus were significantly increased in all groups, compared to the control group. The counts of pCREB-positive cells in the piriform cortex were significantly increased in the acupuncture and 100Hz EA group, compared to the control group. Conclusion : We conclude that acupuncture and EA may affect neuronal cell proliferation, differentiation and plasticity in the brain.

• Clinical and Experimental Reproductive Medicine
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• 제25권3호
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• pp.305-313
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• 1998

Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle. However there is little information about the effect of estrogen (E) and progesterone (P) on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E and/or P-induced expression of c-Fos, CREB, ATF and HSP70 in rat uterus. Rats, ovariectomized (OVX) for two weeks, were divided into 6 experimental groups, 1) OVX, 2) OVX+V, 3) OVX+E, 4) OVX+P, 5) OVX+E+V, 6) OVX+E+P, and western blotting assay for nuclear extract and immunohistochemical staining were carried out for each experimental group. Treatment of E $(10{\mu}g)$ showed to increase the expression of c-Fos, CREB, ATF, and HSP70, and maximal expression was occured at $3\sim6$ hr after E administration. P (1mg) also increased, but much less than E, the expression of c-Fos, ATF, and HSP70. However, P did not reveal any effect on the expression CREE. P treatment 4 hr after E injection decreased c-Fos, CREB, and ATF expression, but did not show any change in the E-induced HSP70 expression. In immunohistochemical study c-Fos-, CREB-, and ATF-immunoreactivities were confined to the cells of luminal epithelium of uterine endometrium. These results suggest that proliferation and differentiation of rat uterus during reproductive cycle may mediated via expression of transcription factors, such as c-Fos, CREB, ATF, and HSP70.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.113-117
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• 2008

Morphine is a potent analgesic with significant abuse potential, because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. Previously, we have reported the inhibitory effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. The present study was employed whether p-CREB expression is involved in the inhibitory effect of MCJ on the morphine-induced CPP in the mouse hippocampus. Repeated administration of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of p-CREB was increased in the dentate gyrus of the hippocampus that had undergone morphineinduced CPP. This increase of expression was significantly inhibited by administration of MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of p-CREB expression in the mouse dentate gyrus of the hippocampus.

• BMB Reports
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• 제41권3호
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• pp.242-247
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• 2008

MSS, a comprising mixture of maesil (Prunus mume Sieb. et Zucc) concentrate, disodium succinate and Span80 (3.6 : 4.6 : 1 ratio) showed a significant improvement of memory when daily administered (460 mg/kg day, p.o.) into the normal rats for 3 weeks. During the spatial learning of 4 days in Morris water maze test, both working memory and short-term working memory index were significantly increased when compared to untreated controls. We investigated a molecular signal transduction mechanism of MSS on the behaviors of spatial learning and memory. MSS treatment increased hippocampal mRNA levels of NR2B and TrkB without changes of NR1, NR2A, ERK1, ERK2 and CREB. However, the protein levels of pERK/ERK and pCREB/CREB were all significantly increased to $1.5{\pm}0.17$ times. These results suggest that the improving effect of spatial memory for MSS is linked to MAPK/ERK signaling pathway that ends up in the phosphorylation of CREB through TrkB and/or NR2B of NMDA receptor.

• BMB Reports
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• 제42권3호
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• pp.142-147
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• 2009

Small-molecule inhibitors of protein kinases have contributed immensely to our understanding of biological signaling path-ways and have been exploited therapeutically for the treatment of cancers and other disease states. The pyridinyl imidazole compounds SB 203580 and SB 202190 were identified as ATP competitive antagonists of the p38 stress-activated protein kinases and have been widely used to elucidate p38-dependent cellular processes. Here, we identify SB 203580 and SB 202190 as potent inhibitors of stress-induced CREB phosphorylation on Serine 111 (Ser-111) in intact cells. Unexpectedly, we found that the inhibitory activity of SB 203580 and SB 202190 on CREB phosphorylation was independent of p38, but instead correlated with inhibition of casein kinase 1 (CK1) in vitro. The inhibition of CK1-mediated CREB phosphorylation by concentrations of pyridinyl imidazoles commonly employed to suppress p38, suggests that in some cases conclusions of p38-dependence derived solely from the use of these inhibitors may be invalid.