• 생명과학회지
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• 제24권7호
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• pp.762-768
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• 2014

Starvation에 의해서 down-regulation 되는 유전자 10개를 얻었다(Comt, RGN, Scd1, Temt, Idi1, Fabp5, Car3, Cyp2c70, Pinx1, Poldip3). 이들은 starvation에 의한 대사변화의 대부분은 liver와 관련된 것으로 볼 수 있다. Starvation중에 물 공급은 암수 동일하게 apoptosis, autophage, endoplasmic reticulum quality control (ERQC)유도에 영향을 미치지 않았다. 이 같이 starvation에 의해서 down-regulation되는 유전자발현조절이 liver에 국한된 것이라기보다는 개체의 항상성유지에 관련 많은 pathway가 관련되어있는 것으로 판단된다. 장기간의 간혈 starvation은 glucose소비가 많은 brain과 면역기능조절에 중요한 thymus의 정상기능에 영향을 미칠 수 있는 것으로 보인다. 유전자 Scd1의 경우는 ♀보다가 ♂이 민감한 반응을 보이는 것으로 보아 ♀/♂의 성 특이적인 대사에 starvation과 NaCl이 밀접한 관계가 있는 것으로 보인다. Starvation시 물 공급도 중요하지만 개체의 항상성유지에 NaCl공급이 중요하다는 결과를 얻었다.

• Environmental Analysis Health and Toxicology
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• 제22권3호
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• pp.227-233
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• 2007

It has been reported that hepatic glutathione (GSH) levels are decreased in diabetic patients, and glucagon increases hepatic efflux of GSH into blood. The signaling pathways responsible for mediating the glucagon effects on GSH efflux, however, are unknown. The signaling pathways involved in the regulation of GSH efflux in response to glucagon and insulin were examined in primary cultured rat hepatocytes. The GSH concentrations in the culture medium were markedly increased by the addition of glucagon, although cellular GSH levels are significantly decreased by glucagon. Insulin was also increased the GSH concentrations in the culture medium, but which is reflected in elevations of both cellular GSH and protein. Treatment of cells with 8-bromo-cAMP or dibutyryl-cAMP also resulted in elevation of the GSH concentrations in the culture medium. Pretreatment with H89, a selective inhibitor of protein kinase A, before glucagon addition markedly attenuated the glucagon effect. These results suggest that glucagon changes GSH homeostasis via elevation of GSH efflux, which may be responsible for decrease in hepatic GSH levels observed in diabetic condition. Furthermore, the present study implicates cAMP and protein kinase A in mediating the effect of glucagon on GSH efflux in primary cultured rat hepatocytes.

• Toxicological Research
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• 제14권4호
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• pp.507-513
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• 1998

The purpose of this study was to clarify the effect of silica on cytosolic free calcium mobilization and cell injury in primary cultured rat hepatocytes. Cytosolic free calcium concentration ([Ca$^{2+}$]) was measured employing calcium sensitive fluorescent dye, Fura-2 / AM, and cell injury was evaluated by determination of cellular ATP contents. Silica increased [Ca$^{2+}$], in a concentration-dependent manner in hepatocytes (10$^{-5}$ ~10$^{-2}$ M). Silica caused a biphasic increase in [Ca$^{2+}$], which was composed of an initial rapid rise and following sustained phase. $Ca^{2+}$ removal from the medium resulted in abolishment of initial and sustained phase of silica (10$^{-2}$ M)-induced [Ca$^{2+}$], in hepatocytes. The pretreatment with nifedipine (1 $\mu$M) attenuated silica-induced [Ca$^{2+}$], increases. Silica decreased cellular ATP contents in a dose-dependent manner. This silica-induced cell injury was attenuated by the pretreatment with EGTA (100 $\mu$M) and nifedipine (1 $\mu$M). This study suggests that the elevation of [Ca$^{2+}$], caused by silica may be due mainly to influx through a plasma membrane $Ca^{2+}$ channel and hepatotoxicity by silica relate with alteration of calcium homeostasis.ium homeostasis.

• Molecules and Cells
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• 제28권5호
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• pp.479-487
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• 2009

Glutathione reductase (GR) is an enzyme that recycles a key cellular antioxidant molecule glutathione (GSH) from its oxidized form (GSSG) thus maintaining cellular redox homeostasis. A recombinant plasmid to overexpress a GR of Brassica rapa subsp. pekinensis (BrGR) in E. coli BL21 (DE3) was constructed using an expression vector pKM260. Expression of the introduced gene was confirmed by semi-quantitative RT-PCR, immunoblotting and enzyme assays. Purification of the BrGR protein was performed by IMAC method and indicated that the BrGR was a dimmer. The BrGR required NADPH as a cofactor and specific activity was approximately 458 U. The BrGR-expressing E. coli cells showed increased GR activity and tolerance to $H_2O_2$, menadione, and heavy metal ($CdCl_2$, $ZnCl_2$ and $AlCl_2$)-mediated growth inhibition. The ectopic expression of BrGR provoked the co-regulation of a variety of antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase. Consequently, the transformed cells showed decreased hydroperoxide levels when exposed to stressful conditions. A proteomic analysis demonstrated the higher level of induction of proteins involved in glycolysis, detoxification/oxidative stress response, protein folding, transport/binding proteins, cell envelope/porins, and protein translation and modification when exposed to $H_2O_2$ stress. Taken together, these results indicate that the plant GR protein is functional in a cooperative way in the E. coli system to protect cells against oxidative stress.

• Journal of Microbiology and Biotechnology
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• 제18권2호
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• pp.242-247
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• 2008

In the fungal pathogen Candida albicans, the yeast-to-hyphal transition occurs in response to a broad range of environmental stimuli and is considered to be a major virulence factor. To address whether the zinc homeostasis affects the growth or pathogenicity of C. albicans, we functionally characterized the zinc-finger protein Csr1 during filamentation. The deduced amino acid sequence of Csr1 showed a 49% similarity to the zinc-specific transcription factor, Zap1 of Saccharomyces cerevisiae. Sequential disruptions of CSR1 were carried out in diploid C. albicans. The csr1/csr1 mutant strain showed severe growth defects under zinc-limited growth conditions and the filamentation defect under hypha-inducing media. The colony morphology and the germ-tube formation were significantly affected by the csr1 mutation. The expression of the hyphae-specific gene HWP1 was also impaired in csr1/csr1 cells. The C. albicans homologs of ZRTl and ZRT2, which are zinc-transporter genes in S. cerevisiae, were isolated. High-copy number plasmids of these genes suppressed the filamentation defect of the csr1/csr1 mutant strain. We propose that the filamentation phenotype of C. albicans is closely associated with the zinc homeostasis in the cells and that Csr1 plays a critical role in this regulation.

• Asian-Australasian Journal of Animal Sciences
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• 제23권5호
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• pp.588-597
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• 2010

We investigated the effect of quercetin on growth and plasma cholesterol level and the effects of quercetin pretreatment (Diet 1, 0%; Diet 2, 0.25%; and Diet 3, 0.5% quercetin) for 30 and 60 days on oxidative stress induced by hypo-osmotic conditions (17.5, 8.75, and 4 psu) in olive flounder. The weights of flounder were higher with Diet 3 than with Diet 1 and 2, which indicated that a high concentration (Diet 3) of quercetin was very effective in growth. Total cholesterol levels were lower with Diets 2 and 3 than with Diet 1, leading us to hypothesize that quercetin removed low-density lipoproteins from circulation and thereby reduced total cholesterol. To understand the antioxidant role of quercetin, we measured the mRNA expression and activities of superoxide dismutase (SOD) and catalase (CAT) and the $H_2O_2$ concentration in quercetin-treated flounder exposed to osmotic stress. The $H_2O_2$ concentration and the SOD and CAT expression and activity levels were lower in flounder fed with Diets 2 and 3 than with Diet 1, suggesting that quercetin directly scavenges reactive oxygen species to reduce oxidative stress. Furthermore, the plasma lysozyme activity and osmolality were higher with Diets 2 and 3 than with Diet 1, indicating that quercetin increases immune function and helps to maintain physiological homeostasis. Plasma cortisol was lower with Diets 2 and 3 than with Diet 1, suggesting the quercetin protects against stress. These results indicate that quercetin has hypocholesterolemic and antioxidant effects, increases immune function, and acts to maintain physiological homeostasis.

• Childhood Kidney Diseases
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• 제20권1호
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• pp.11-17
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• 2016

Appropriate control of diet and water intake is important for maintaining normal blood pressure, fluid and electrolyte homeostasis in the body. It is relatively understood that the amount of sodium and potassium intake directly affects blood pressure and regulates ion transporters; Na and K channel functions in the kidney. However, little is known about whether diet and water intake regulates Aquaporin (AQP) function. AQPs, a family of aquaporin proteins with different types being expressed in different tissues, are important for water absorption by the cell. Water reabsorption is a passive process driven by osmotic gradient and water permeability is critical for this process. In most of the nephron, however, water reabsorption is unregulated and coupled to solute reabsorption, such as AQP1 mediated water absorption in the proximal tubule. AQP2 is the only water channel founded so far that can be regulated by hormones in the kidney. AQP2 expressed in the apical membrane of the principal cells in the collecting tubule can be regulated by vasopressin (antidiuretic hormone) controlling the final volume of urine excretion. When vasopressin binds to its receptor on the collecting duct cells, it stimulates the translocation of AQP2 to the membrane, leading to increased water absorption via this AQP2 water channel. However, some studies also indicated that the AQP2 is also been regulated by vasopressin independent mechanism. This review is focused on the regulation of AQP2 by diet and the amount of water intake on salt and water homeostasis.

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권2호
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• pp.43-45
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• 2016

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. Serotonin is among those traditional pharmacological targets for anti-obesity treatment because central 5-HT functions as an anorexigenic neurotransmitter in the brain. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Fat specific Tph1 knock-out (Tph1 FKO) mice exhibit similar phenotypes as mice with pharmacological inhibition of 5-HT synthesis, suggesting the localized effects of 5-HT in adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure in BAT and Htr2a KO mice exhibit the decreased lipid accumulation in WAT. These data suggest the clinical significance of the peripheral serotonergic system as a new therapeutic target for anti-obesity treatment.

• 생물정신의학
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• 제22권2호
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• pp.40-46
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• 2015

Neuroglial cells are fundamental for brain homeostasis and defense to intrinsic or extrinsic changes. Loss of their function and over-reactivity to stimuli contribute to the aging of brain. Alzheimer's disease (AD) could be caused by more dramatic response in neuroglia associated with various chemokines and cytokines. Neuroglia of the AD brain shares some phenotypes with aging neuroglia. In addition, neuroglial activation and neuroinflammation are commonly showed in neurodegeneration. Thus neuroglia would be a promising target for therapeutics of AD.

• 한국발생생물학회지:발생과생식
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• 제16권3호
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• pp.169-175
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• 2012

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability and autism. The genetic cause is the absence of UBE3A, an E3 ubiquitin ligase, from the maternal chromosome which can arise from multiple origins. Recently discovered targets of Ube3a are important for activity dependent changes in synaptic transmission and spine morphology. Plasticity studies in an AS mouse model is important for basic plasticity research with regard to understanding protein homeostasis as well as the search for therapeutic targets for the patients. The progress on synaptic plasticity from this unique disorder is reviewed.