• 약학회지
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• 제41권1호
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• pp.81-85
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• 1997

Ceramide has been suggested as an important mediator of the effects of extracellular agonists on cell growth inhibition, differentiation, apoptosis. However the biochemical sign aling mechanism involved in transducing the effects of ceramide on leukemia cell differentiation is still unclear. In these respects, we examined the regulatory effects of ceramide on c-jun gene expression during differentiation. In U-937 cells. ceramide increased c-jun mRNA levels in a time-dependent manner. The half life, of c-jun mRNA was 30 min. In contrast, inhibition of protein synthesis with cycloheximide in the absence, of transcription with actinomycin D increased the half-life of c-jun mRNA in ceramide-treated U-937 cells to more than 90 min. In order to examine whether ceramide-inhibited c-jun gene expression is regulated through ceramide-activated protein phosphatase (CAPP), a direct target for the action of ceramide, okadaic acid were treated to the cells. Okadaic acid inhibited enhancement of c-jun mRNA induced by C2-ceramide in a dose-dependent manner. These results suggested that ceramide increases c-jun mRNA level during differentiation in U-937 cells and regulates the gene expression on posttranscriptional level. In addition, we provide the evidence that CAPP is involved in ceramide-induced c-jun gene expression in U-937 cells.

• Molecules and Cells
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• 제24권2호
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• pp.210-214
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• 2007

The 90-kDa heat shock protein (HSP90) normally functions as a molecular chaperone participating in folding and stabilizing newly synthesized proteins, and refolding denatured proteins. The HSP90 inhibitor geldanamycin (GA) occupies the ATP/ADP binding pocket of HSP90 so inhibits its chaperone activity and causes subsequent degradation of HSP90 client proteins by proteasomes. Here we show that GA reduces the level of endogenous c-Jun in human embryonic kidney 293 (HEK293) cells in a time and dose dependent manner, and that this decrease can be reversed by transfection of HSP90 plasmids. Transfection of HSP90 plasmids in the absence of GA increases the level of endogenous c-Jun protein, but has no obvious affect on c-Jun mRNA levels. We also showed that HSP90 prolongs the half-life of c-Jun by stabilizing the protein; the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) blocks the degradation of c-Jun promoted by GA. Transfection of HSP90 plasmids did not obviously alter phosphorylation of c-Jun, and a Jun-2 luciferase activity assay indicated that over-expression of HSP90 elevated the total protein activity of c-Jun in HEK293 cells. All our evidence indicates that HSP90 stabilizes c-Jun protein, and so increases the total activity of c-Jun in HEK293 cells.

• 한국섬유공학회:학술대회논문집
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• 한국섬유공학회 1986년도 학술발표초록집
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• pp.46-46
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• 1986

• BMB Reports
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• 제43권1호
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• pp.57-61
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• 2010

Activator protein-1 can induce either cell survival or death, which is controlled by opposing effects of different Jun members. It is generally accepted that c-Jun is pro-apoptotic, but that JunD is anti-apoptotic in stress-exposed cells. Additionally, although there are reports suggesting that JunB plays a protective role, its role in stress-induced apoptosis remains unclear. Here, we investigated the role of JunB in $H_2O_2$-induced cell death using cells that over-expressed the protein or were transfected with si-JunB. Inhibition of JunB expression accelerated $H_2O_2$-mediated loss of mitochondrial membrane potential (MMP) and cytotoxicity. Conversely, over-expression of JunB protein led to significant inhibition of the MMP loss and cell death. The increase in JunB expression also attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl-2 reduction that occurred following $H_2O_2$ exposure. These results suggest that JunB can signal survival against oxidant-mediated cell death by suppressing mitochondrial stress.

• Clinical and Experimental Reproductive Medicine
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• 제26권2호
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• pp.149-156
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• 1999

포유류의 자궁조직은 발정주기를 통하여 역동적으로 변화하고 있으며 이러한 자궁조직의 분화는 시상하부-뇌하수체-생식소를 잇는 축에 의해 조절되는 스테로이드 호르몬에 의해 이루어진다. 그러나 에스트로겐 (E)이 어떤 유전자를 발현하여 자궁 내의 변화를 일으키는지는 아직 자세히 알려지지 않고 있다. 본 연구는 난소를 절제한 성숙한 흰쥐에 E을 처리한 후 자궁조직 내에서 c-fos, c-jun 및 hsp25 mRNA의 발현 변화를 Northern blot analysis방법을 사용하여 연구한 것이다. c-fos및 c-jun 암원유전자의 mRNA발현은 E처리 후 1시간 이전부터 증가하기 시작하며, 3시간 이내에 최고치에 도달한 후 급격히 감소하여 기저수준으로 되돌아갔다. 반면에 hsp25 mRNA수준은 E처리 후 3시간 대에서 최고치를 나타내나 증가된 발현량이 서서히 감소하며 12시간이 지난 후 까지도 정상대조군에 비해 높은 수준으로 유지되었다. 이러한 E의 영향이 선별적인지를 검증하기 위하여 E의 길항제인 tamoxifen을 사전처리하고 E을 추가로 처리하여 c-fos, c-jun및 hsp25 mRNA의 발현이 최고치에 이르렀던 3시간대에 자궁조직을 얻어 각각의 유전자 발현량을 조사한 결과 E에 의해 증가되었던 c-fos, c-jun 및 hsp25 mRNA의 수준이 억제됨을 확인하였다. 이러한 결과는 E이 자궁조직에 영향을 미치는데 초기의 일시적인 변화를 보이는 암원유전자인 c-fos 및 c-jun이 중요한 역할을 하리라는 것을 시사하며 hsp25의 경우는 좀더 늦은 반응에 관여하거나 c-fos및 c-jun에 의하여 간접적으로 조절을 받을 수도 있음을 보여 주는 것으로 사료된다.

• 대한한의학방제학회지
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• 제10권1호
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• pp.73-80
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• 2002

We have examined the purgative effect of three Jechun-jun formulas in sprague dawley(SD) rat. Three jechun-jun formulas were Jechun-jun(Sample I ) and augmented Jechun-jun(Sample II) and augmented Jechun-jun add rhubarb(sample III ). We examined the amount and the humidity of feces in rat. The experimental animals were devided into four groups. as control group and three Jechun-jun (sample I, II, III). We administerd the water extract of sample I, II, III to rat per oral for 8days long. After every 24hours measured the amount of wet feces from rats in metabolic cage. Humidity rate of feces from rat was at first measure wet feces for 24hours (W) and measure dried feces (W1) and then we consider W-W1 as humidity. High humidity rate means constipation changes into moistening stool. The amount of wet feces and humidity rate of feces in rats were increased in sample I, II, III. Sample I has highest humidity rate of feces. so showed strong moistening effect. Sample II has mild effect in treating constipation. sample III has most amount of wet feces. in conclusion Jechun-jun has an effect of moistening stool. and augmented Jechun-jun add rhubarb has strong purgative effect.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.195-204
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• 2021

Cereblon (CRBN), a substrate receptor of cullin 4-RING E3 ligase (CRL4) regulates the ubiquitination and degradation of c-Jun, mediating the lipopolysaccharide-induced cellular response. However, the upstream signaling pathway that regulates this process is unknown. In this study, we describe how endoplasmic reticulum (ER) stress reversely regulates sequestosome-1 (p62)and c-Jun protein levels. Furthermore, our study reveals that expression of p62 attenuates c-Jun protein levels through the ubiquitinproteasome system. Conversely, siRNA knockdown of p62 elevates c-Jun protein levels. Immunoprecipitation and immunoblotting experiments demonstrate that p62 interacts with c-Jun and CRBN to form a ternary protein complex. Moreover, we find that CRBN knockdown completely abolishes the inhibitory effect of p62 on c-Jun. Using brefeldin A as an inducer of ER stress, we demonstrate that the p62/c-Jun axis participates in the regulation of ER stress-induced apoptosis, and that CRBN is required for this regulation. In summary, we have identified an upstream signaling pathway, which regulates p62-mediated c-Jun degradation. Our findings elucidate the underlying molecular mechanism by which p62/c-Jun axis regulates the ER stress-induced apoptosis, and provide a new molecular connection between ER stress and apoptosis.

• 생명과학회지
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• 제26권12호
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• pp.1383-1391
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• 2016

타목시펜과 같은 항에스트로젠은 ER 양성의 초기 유방암 환자에게 사용되고 있다. 그러나 대부분의 환자에서 이 항에스트로젠에 대한 내성 발현은 불가피하게 발생한다. BCAR3 유전자는 사람의 에스트로젠 의존성 유방암에서 tamoxifen 내성유도를 야기하는 단백질로 발견되었다. 우리들은 이전에 이 BCAR3 유전자가 세포주기 진행과 EGF와 인슐린에 의한 DNA 합성 신호전달경로를 조절한다고 보고하였다. 본 연구에서는, 비종양성 정상적인 인간유방상피세포인 MCF-12A세포에서 c-Jun 전자의 조절에 대한 BCAR3유전자의 기능적인 역할을 조사하였다. BCAR3의 일시적인 발현 또는 지속적인 발현이 c-Jun mRNA와 단백질의 발현을 증가하는 것을 발견하였다. 또한 BCAR3 발현 유전자의 미세주사에 의해 세포 증식이 증가하였다. 이 c-Jun의 발현 증가는 promoter의 활성화를 통해 일어난다. 또한 BCAR3에 의한 c-Jun 발현 유도가 억제성 Ras, Rac, Rho에 의해 억제되었다. 다음으로 EGF 성장인자에 의한 c-Jun 발현 유도에 대한 BCAR3의 영향을 단일 세포 미세주사법에 의해 조사하였다. BCAR3 항체, BCAR3의 siRNA와 같은 BCAR3의 기능을 억제할 수 있는 물질들을 세포로 미세주사하면 EGF에 의한 c-Jun의 발현을 억제하였지만, IGF-1 성장인자에 의한 c-Jun 발현은 억제하지 않았다. 이러한 결과들로부터 BCAR3는 c-Jun 단백질 발현 유도와 세포 증식에 중요한 역할을 하며, 여기에는 Ras, Rac, Rho와 같은 GTPase들이 필요하다는 것을 발견하였다.

• 동의생리병리학회지
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• 제24권1호
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• pp.143-151
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• 2010

In Vivo and In vitro antispasmodic effects of Jun-Si-Baek-Chul-San, a Traditional Korean Polyherbal Medicineconsisted of 7 types of herbs were observed in the present study. To clarify the effects of Jun-Si-Baek-Chul-San, on accelerating small intestinal movement induced by the stimulation of cholinergic neurotransmission, we evaluated the effects of Jun-Si-Baek-Chul-San on In vivo carbachol (an acetylcholinergic agent)-accelerated mice small intestinal transit and on In vitro contractions induced by low-frequency electrostimulation, KCl, histamine or acetylcholine using isolated guinea pig ileum. To induce the acceleration of mice small intestinal transit, Carbachol 1 mg/kg was once subcutaneously dosed 15min before last administration of the test drugs. In the present study, Jun-Si-Baek-Chul-San 500, 250 and 125 mg/kg or domperidone 20 mg/kg were orally pretreated on the carbachol-accelerated mice small intestinal transit once a day for 7 days and the small intestinal transit rateof activated charcoal powder were monitored. In vitro assays, Jun-Si-Baek-Chul-San1, 0.1, 0.01 and 0.001 mg/ml or domperidone $2{\times}10^{-5}M$ were treated 10min before ileal contraction was induced by filed stimulation, acetylcholine, KCl and histamine, and the % changes of contractions were observed compared to the treatment of inducer alone. In spontaneous contraction, the % changes of contractions were observed compared to treatment of vehicle alone at 10min after Jun-Si-Baek-Chul-San or domperidone treatment. The efficacy of Jun-Si-Baek-Chul-San was compared to those of domperidone. High concentration, 1 mg/ml of Jun-Si-Baek-Chul-San was found to decrease the spontaneous contraction of the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San decrease contractions induced by electrostimulation, acetylcholine, histamine and KCl in the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San effectively inhibited the accelerated small intestinal movement induced by carbachol stimulation of cholinergic neurotransmission in In vivo. Based on the results, although the exact molecular or action mechanism and which herbs or compound in Jun-Si-Baek-Chul-San are responsible for actions, it was concluded that Jun-Si-Baek-Chul-San normalization in the accelerated intestinal motility might be interfere with a variety of muscarinic, adrenergic and histaminic receptor activities or with the mobilization of calcium ions required for smooth muscle contraction non-specificly. Therefore, it is expected that Jun-Si-Baek-Chul-San will be promising as a prescription of clinical treatment of digestive tract disorders such as accelerated the motility of intestine, diarrhea or intestinal painful contractions.

• 한국콘텐츠학회논문지
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• 제11권1호
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• pp.245-253
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• 2011

본 연구는 흰쥐 해마에서 c-fos, c-jun 발현에 수영운동이 미치는 영향을 규명하는 것이다. 실험 대상은 생후 4주 흰쥐(4-weeks aged rat)와 생후 4개월 흰쥐(16-weeks aged rat)를 사용하였다. 두 집단 모두 대조군, 실험군으로 분류하였으며, 수영 운동은 1일 1시간 하였으며 1, 3, 7일 실시한 후 다음과 같은 결과를 얻을 수 있었다. c-fos, c-jun 단백질 발현에 있어서 두 실험군 모두 운동 1, 3, 7일에서 유의하게 증가하였으며, 7일이 가장 많이 증가하였고 3일, 1일 순으로 증가 하였다. 두 실험군을 비교했을 때 생후 4주 그룹이 4개월 그룹보다 더 많은 c-fos, c-jun 단백질 발현을 보여 통계적으로 유의하게 나타났다. 따라서 수영 운동이 해마에서 c-fos, c-jun 단백질 발현을 증가시키는 것으로 나타나 운동의 효과가 있는 것으로 보이며, 수영 운동에 의한 초기발현 유전자의 활성화로 인하여 학습 및 기억과 같은 인식 기능을 예방 및 개선시키며 신경성장 및 회복에 긍정적인 효과가 있는 것으로 보인다.