• 생명과학회지
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• 제25권2호
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• pp.231-236
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• 2015

Angiotensin II (AngII)는 혈관평활근세포의 수축을 통해 혈관을 수축시키는 강력한 작용을 나타낼 뿐만 아니라 혈관세포의 성장 등에 중요한 역할을 한다. 본 연구에서는 AngII에 의해 형성되는 활성산소가 phosphatidylinositol 3-kinase (PI3K)에 유리되는 칼슘에 의해 조절된다는 것을 검증하였다. 쥐의 대동맥으로부터 분리된 혈관평활근세포에서 AngII에 의해 활성산소가 농도 의존적, 그리고 시간 의존적으로 형성됨을 관찰하였다. AngII에 의해 형성되는 활성산소는 PI3K의 억제제에 의해 봉쇄되었으나 EKR의 억제제에 의해서는 봉쇄되지 않음을 알 수 있었다. AngII에 의해 유리되는 칼슘은 L-type 칼슘이온통로 봉쇄제인 Nifedipine 또는 배양액에 칼슘이 제거된 환경에서 억제됨을 확인할 수 있었다. 마지막으로 AngII에 의해 형성되는 활성산소는 배양액에 칼슘이 없는 조건이나 L-type 칼슘이온통로 억제제를 전처리 하였을 경우 억제되는 것을 확인하였다. 이러한 결과들을 바탕으로 쥐의 대동맥으로부터 분리된 혈관평활근세포에서 AngII에 의한 활성산소의 형성은 PI3K/L-type 칼슘이온통로를 통한 기전을 통해 조절됨을 제안한다.

• BMB Reports
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• 제56권5호
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• pp.314-319
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• 2023

Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-β (IFN-β) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression. Another study also reported its significant protective effect against acute respiratory distress syndrome, a complication of severe sepsis, in human patients. However, the IFN-β effect cannot solely be explained by SIRT1-mediated immunosuppression, since sepsis induces immunosuppression in patients. Here, we show that IFN-β, in combination with nicotinamide riboside (NR), alleviates sepsis by blocking endothelial damage via SIRT1 activation. IFN-β plus NR protected against cecal ligation puncture-(CLP)-induced sepsis in wild-type mice, but not in endothelial cell-specific Sirt1 knockout (EC-Sirt1 KO) mice. IFN-β upregulated SIRT1 protein expression in endothelial cells in a protein synthesis-independent manner. IFN-β plus NR reduced the CLP-induced increase in in vivo endothelial permeability in wild-type, but not EC-Sirt1 KO mice. IFN-β plus NR suppressed lipopolysaccharide-induced up-regulation of heparinase 1, but the effect was abolished by Sirt1 knockdown in endothelial cells. Our results suggest that IFN-β plus NR protects against endothelial damage during sepsis via activation of the SIRT1/heparinase 1 pathway.

• Journal of Ginseng Research
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• 제47권6호
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• pp.784-794
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• 2023

Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Lepr^db/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.1-8
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• 2000

To investigate the contributions of intrinsic membrane properties to the spontaneous activity of medial vestibular nucleus (MVN) neurons, we assessed the effects of blocking large and small calcium-activated potassium channels by means of patch clamp recordings. Almost all the MVN neurons recorded in neonatal $(P13{\sim}P17)$ rat were shown to have either a single deep after-hyperpolarization (AHP; type A cells), or an early fast and a delayed slow AHP (type B cells). Among the recorded MVN cells, immature action potential shapes were found. Immature type A cell showed single uniform AHP and immature B cell showed a lack of the early fast AHP, and the delayed AHP was separated from the repolarization phase of the spike by a period of isopotentiality. Application of apamin and charybdotoxin (CTX), which selectively block the small and large calcium-activated potassium channels, respectively, resulted in significant changes in spontaneous firings. In both type A and type B cells, CTX (20 nM) resulted in a significant increase in spike frequency but did not induce bursting activity. By contrast, apamin (300 nM) selectively abolished the delayed slow AHP and induced bursting activity in type B cells. Apamin had no effect on the spike frequency of type A cells. These data suggest that there are differential roles of apamin and CTX sensitive potassium conductances in spontaneous firing patterns of MVN neurons, and these conductances are important in regulating the intrinsic rhythmicity and excitability.

• IMMUNE NETWORK
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• 제13권6호
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• pp.249-256
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• 2013

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

• Molecules and Cells
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• 제28권5호
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• pp.489-494
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• 2009

We have previously shown that the down-regulation of protein kinase CKII activity is tightly associated with cellular senescence of human fibroblast IMR-90 cells. Here, we examined the roles of p53 and $p21^{Cip1/WAF1}$ in senescence development induced by CKII inhibition using wild-type, isogenic p53-/- and isogenic p21-/- HCT116 human colon cancer cell lines. A senescent marker appeared after staining for senescence-associated ${\beta}$-galactosidase activity in wild-type HCT116 cells treated with CKII inhibitor or $CKII{\alpha}$ siRNA, but this response was almost abolished in p53- or $p21^{Cip1/WAF1}$-null cells. Increased cellular levels of p53 and $p21^{Cip1/WAF1}$ protein occurred with the inhibition of CKII. CKII inhibition upregulated p53 and $p21^{Cip1/WAF1}$ expression at post-transcriptional level and transcription level, respectively. RB phosphorylation significantly decreased in cells treated with CKII inhibitor. Taken together, this study shows that the activation of the $p53-p21^{Cip1/WAF1}$ pathway acts as a major mediator of cellular senescence induced by CKII inhibition.

• 교육시설 논문지
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• 제19권3호
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• pp.21-31
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• 2012

According to the decrease in birth rate and reduction of population in rural area, primary schools have brought about many problems for decrease of number of student, and environment of education have became deteriorated. Accordingly, primary schools be required improvement, and it should be altered placement of schools because it change number of student, distance and time of attending school, and formation of school zone are changed by alternating of human and physical environment. Merger and abolition of primary school is inevitable for change of placement standard to primary school and qualitative improvement of environment of education in rural area. This study suggests the effective space planning methods for unified school and appropriate utilization alternatives for closed school following after the merger and abolition of small rural schools. In doing so, it explores the present models of merger and abolition through analysis of all sort of actual condition and the possibilities for various utilizations of the abolished schools. It proposes a classroom-operation type fused the comprehensive class and departmental class system for merged primary schools in rural area. It also suggests the re-use methods of closed school facilities for students and community. Finally, it emphasizes that in order to success the policy of the merger and abolition of small schools, it be attributed to the social-cultural environment based on local residents and community and required provision of a variety of utilization plans reflecting local specifics and guarantee of local residents' participation and selection.

• The Korean Journal of Physiology and Pharmacology
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• 제9권2호
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• pp.87-94
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• 2005

It is not clear whether $Ca^{2+}-induced$ $Ca^{2+}$ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that $Ca^{2+}$ entry via voltage-gated L-type $Ca^{2+}$ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR $Ca^{2+}$ release in the regulation of ANP release and whether $Ca^{2+}$ entry via L-type $Ca^{2+}$ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR $Ca^{2+}$ release, increased atrial myocytic ANP release ($8.69{\pm}3.05$, $19.55{\pm}1.09$, $27.31{\pm}3.51$, and $18.91{\pm}4.76$% for 1, 2, 3, and $6{\mu}M$ ryanodine, respectively; all P<0.01) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR $Ca^{2+}$ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type $Ca^{2+}$ channel with nifedipine abolished ryanodine-induced increase in ANP release ($0.69{\pm}5.58$% vs. $27.31{\pm}3.51$%; P＜0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that $Ca^{2+}$-induced $Ca^{2+}$ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

• 대한미생물학회지
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• 제15권1호
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• pp.63-69
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• 1980

C. parvum은 면역학적(免疫學的) 연구(硏究)에 immunomodulating agent로서 광범위(廣範圍)하게 이용(利用)되고 있기 때문에 C. parvum이 SRBC에 대(對)한 면역반응(免疫反應)에 미치는 영향(影響) 및 그 기전(機轉)을 알아보고자 본(本) 실험(實驗)을 실시(實施)한 결과(結果) 다음과 같은 성적(成績)을 얻었다. C. parvum이 SRBC에 대(對)한 DTH에 미치는 영향(影響)은 C. parvum 투여시기(投與時期)에 따라 상이(相異)한 결과(結果)를 나타내었는데 C. parvum을 SRBC로 면역전(免疫前)에 정맥내(靜脈內)로 투여(投與)했을 때 유의(有意)있는 지연성(遲延性) 과민반응(過敏反應)(DTH)의 감소(減少)를 보였으며 이러한 현상(現象)은 cyclophosphamide로 처리(處理)했을 때 완전(完全)히 소실(消失)되었다. 또한 C. parvum은 S. typhimurium의 증식(增殖)을 억제(抑制)하고 비장(脾臟) 및 간장종대(肝臟腫大)를 야기(惹起)시켰는데 이러한 사실(事實)로 미루어 C. Parvum의 DTH 감소현상(減少現象)은 suppressor T 세포(細胞) 또는 활성화(活性化)된 대식세포(大食細胞)의 중개(仲介)에 의한 것으로 사료(思料)되었다. C. parvum은 SRBC에 대(對)한 항체가(抗體價)에 유의(有意)있는 영향(影響)을 미치지 못하였다.

• Molecules and Cells
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• 제25권1호
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• pp.105-111
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• 2008

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor $(TGF)-{\beta}1$ led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of $TGF-{\beta}$ receptor I kinase, abolished $TGF-{\beta}1$- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via $TGF-{\beta}$ signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.