• 한국동물학회지
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• 제39권3호
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• pp.266-272
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• 1996

봄에 채집한 참개구리의 난소조각 배양계를 사용하여 난자의 배란과정에 프로스타글란딘과 protein kinase C(PKC)가 관여하는 지를 조사하였다. 난소조각을 배양하면서 뇌하수체추출물(FPH) 혹은PKC의 활성제인 12-O-tetradecanoyl phorbol-13-acetate (TPA)를 처리한 후 배란율과 프로스타글란딘의 생상량을 방사면역측정법으로 조사한 결과 농도에 의존하여 난자의 배란이 유도 되었으며 프로스타글란딘의 생성이 촉진되었다. FPH와 TPA에 의한 배란과 프로스타글란딘 생성은, 4월 보다는 5월에 채집한 개구리에서 훨씬 더 효과적이었다. FPH처리는 프로스타글란딘과 함께 progestreone의 생성을 촉진하였으나 TPA는 progestreone의 생성을 촉진하지는 못하였다. FPH와 TPA에 의한 배란과ㅣ 프로스타글라딘 생성 억제제인 indomethacin에 의해서는 난자의 배랑니 억제되지는 않았다. 이러한 결과들은 참개구리 난자의 배란 과정에 PKC의 활성화가 중요한 역할을 하며, 프로스타글라딘의 생성이 매개할 것으로 생각된다.

• Archives of Pharmacal Research
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• 제19권3호
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• pp.201-206
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• 1996

Nitric oxide (NO) is thought to be a second messenger involved in secretion. Upon stimulating pancreatic acinar cells with cholecystokinin-pancreozymin (CCK-PZ), NO formation has been shown to be associated with increased levels of cGMP (Seo et al., 1995). To elucidate the signaling pathway of VIP-induced enzyme secretion, we investigated the NO and cGMP synthesis steps as potential steps where two signal pathways triggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by treatment with VIP has no relationship with NOS activity and cGMP level. This conclusion was derived from the following findings that VIP treatment of rat pancreatic tissue increased amylase release as well as protein output in a dose- and time-dependent manner, whereas NOS activity and cGMP synthesis were not affected by VIP treatment as monitored by NOS activity assay and determining cGMP level, which was further confirmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases enzyme secretion in rat pancreatic tissue, but the two hormones are different in their mode of action. Together the results suggest that signaling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-induced pathway.

• 대한한의학회지
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• 제19권2호
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• pp.36-49
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• 1998

HERBA SAURURI (HS) has been known to use antiinflammatory drug. To investigated the mechanism of HS-induced NO synthesis, I evaluated the ability of protein kinase C (PKC) inhibitors such as staurosporine (STSN) or polyymyxin B to block HS-induced effects. HS alone had only a small effect, whereas in combination with $rIFN-{\gamma}$, markedly increased NO synthesis in a dose dependent manner. STSN and polymyxin B decreased NO synthesis, which had been induced by $rIFN-{\gamma}$, plus HS. Furthermore, prolonged incubation of the cells with phorbol ester, which down-regulates PKC activity abolished synergistic cooperative effect of HS with $rIFN-{\gamma}$ on NO synthesis. STSN and Polymyxin B potently inhibited HS-induced $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. However, $rIFN-{\gamma}$ plus $TNF-{\alpha}-induced$ NO synthesis was not blocked by STSN or polymyxin B. On the other hand, tyrosine kinase inhibitor, genistein, blocked the NO synthesis and $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. In conlusion, the present results strongly suggest that the capacity of HS to increase NO synthesis from $rIFN-{\gamma}-primed$ macrophages is the result of HS-induced $TNF-{\alpha}$ secretion via the signal transduction pathway of PKC and tyrosine kinase.

• Molecules and Cells
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• 제26권4호
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• pp.323-328
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• 2008

Eukaryotic cells continuously integrate intrinsic and extrinsic signals to adapt to the environment. When exposed to stressful conditions, cells activate compartment-specific adaptive responses. If these are insufficient, apoptosis ensues as an organismal defense line. The mechanisms that sense stress and set the transition from adaptive to maladaptive responses, activating apoptotic programs, are the subject of intense studies, also for their potential impact in cancer and degenerative disorders. In the former case, one would aim at lowering the threshold, in the latter instead to increase it. Protein synthesis, consuming energy for anabolic processes as well as for byproducts disposal, can be a significant source of stress, particularly when difficult-to-fold proteins are produced. Recent work from our and other laboratories on the differentiation of antibody secreting cells, revealed a regulatory circuit that integrates protein synthesis, secretion and degradation (proteostasis), into cell lifespan determination. The apoptotic elimination - after an industrious, yet short lifetime - of terminal immune effectors is crucial to maintain immune homeostasis. Linking proteostasis to cell death, this paradigm might prove useful for biotechnological purposes, and the design of novel anti-cancer therapies.

• 약학회지
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• 제27권4호
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• pp.295-301
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• 1983

Among the many protein modifications methylation is being investigated actively with regard to bacterial chemotaxis, gene regulation, muscle contraction, cytochrome c methylation, and the synthesis of the acyl transporter, carnitine. In this study the activities of protein methylase I, II, and III in pancreatic tissues of rat, mouse, and guinea pig were examined. Furthermore, the effect of cholinergic agents on the activity of protein methylases in pancreatic fragment of guinea pig was also examined in order to test the relationship between protein methylation and pancreatic secretion. The results are as follows. 1) The activities of protein methylases were generally high in pancreatic tissues of guinea pig and mouse but low in the tissue of rat. 2) The cholinergic stimulants, acetylcholine and carbachol at a concentration of $10^{-5}M$ decreased the activities of protein methylase I, II, and III compared with unstimulated control. 3) The inhibitory effect of the cholinergic stimulant on the activities of protein methylases was not blocked by atropine at a concentration of $10^{-5}M$.

• Asian-Australasian Journal of Animal Sciences
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• 제14권9호
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• pp.1331-1341
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• 2001

Dairy cows are prone to fatty liver during the time of periparturient. Despite of the extensive studies, etiology and solutions for fatty liver are still not well known.The liver synthesizes triglycerides (TG) using precursors from bloodstream and secretes TG in form of very low density lipoprotein (VLDL) into bloodstream for the utilization by peripheral tissues. When the amount of TG synthesis exceeds the amount of secretion in VLDL-TG, TG accumulation within the liver occurs. Hepatic VLDL assembly and secretion involve multi-biochemical events.The availabilities of apolipoprotein B (apoB), E (apoE), microsomal triglyceride transfer protein (MTP) and soluble low density lipoprotein (LDL) receptor are now believed to be some of the main regulators for hepatic VLDL assembly and secretion. Studies in transgenic animals show that overexpression of these proteins stimulates VLDL production and secretion, which provides a possibility for alleviating bovine fatty liver by gene therapy. However, many problems remain to be solved to attain this goal. This review focuses on the molecular mechanisms of hepatic VLDL assembly and secretion, and the possibilities and problems of applying the knowledges to solve bovine fatty liver by gene therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제50권4호
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• pp.177-188
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• 2024

The endoplasmic reticulum (ER) is crucial for protein synthesis, transport, and folding, as well as calcium storage, lipid and steroid synthesis, and carbohydrate metabolism. Endoplasmic reticulum stress (ERS) occurs when misfolded or unfolded proteins accumulate in the ER lumen due to increased protein secretion or impaired folding. While the role of ERS in disease pathogenesis has been widely studied, most research has focused on extraoral diseases, leaving the role of ERS in intraoral diseases unclear. This review examines the role of ERS in oral diseases and oral fibrosis pathogenesis. A systematic search of literature through July 2023 was conducted in the MEDLINE database (via PubMed) using specific terms related to ERS, oral diseases, and fibrosis. The findings were summarized in both table and narrative form. Emerging evidence indicates that ERS significantly contributes to the pathogenesis of oral diseases and fibrosis. ERS-induced dysregulation of protein folding and the unfolded protein response can lead to cellular dysfunction and inflammation in oral tissues. Understanding the relationship between ERS and oral disease pathogenesis could offer new therapeutic targets for managing oral health and fibrosis-related complications.

• Molecules and Cells
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• 제44권2호
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Asian-Australasian Journal of Animal Sciences
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• 제28권1호
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• pp.127-134
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• 2015

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.

• The Korean Journal of Physiology and Pharmacology
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• 제15권6호
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• pp.345-351
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• 2011

High glucose leads to physio/pathological alterations in diabetes patients. We investigated collagen production in human gingival cells that were cultured in high concentrations of glucose. Collagen synthesis and secretion were increased when the cells were exposed to high concentrations of glucose. We examined endoplasmic reticulum (ER) stress response because glucose metabolism is related to ER functional status. An ER stress response including the expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol requiring enzyme alpha (IRE-$1{\alpha}$) and phosphoreukaryotic initiation factor alpha (p-eIF-$2{\alpha}$) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-$2{\alpha}$ as well as a transcription factor for collagen, was also phosphorylated and translocalized into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest that high concentrations of glucose-induced collagen are linked to ER stress and the associated phosphorylation and nuclear translocation of ATF-4.