• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.85-90
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• 2005

Diesel exhaust Particles (DEPs) are known to induce allergic responses in airway epithelial cells, such as the production of various cytokines via nuclear factor-kappa B ($NF-{\kappa}B$). However. the intracellular signal transduction pathways underlying this phenomenon have not been fully examined. This study showed that DEP induced $NF-{\kappa}B$ activity via transforming growth factor-${\beta}$ activated kinase 1 (TAK1) and $NF-{\kappa}B$-inducing kinase (NIK) in L2 rat lung epithelial cells. DEP induced the $NF-{\kappa}B$ dependent reporter activity approximately two-to three-fold in L2 cells. However, this effect was abolished by the expression of the dominant negative forms of TAK1 or NIK. Furthermore, it was shown that DEP induced TAK1 phosphorylation in the L2 cells. These results suggest that TAK1 and NIK are important mediators of DEP-induced $NF-{\kappa}B$ activation.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.315-324
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• 2016

Human cardiac fibroblasts (HCFs) have various voltage-dependent $K^+$ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide ($H_2O_2$) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether $H_2O_2$ could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of $H_2O_2$ stimulated $Ca^{2+}-activated$ $K^+$ ($K_{Ca}$) currents but not delayed rectifier $K^+$ or transient outward $K^+$ currents, all of which are VDKCs. $H_2O_2-stimulated$ $K_{Ca}$ currents were blocked by iberiotoxin (IbTX, a large conductance $K_{Ca}$ blocker). The $H_2O_2-stimulating$ effect on large-conductance $K_{Ca}$ ($BK_{Ca}$) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated $BK_{Ca}$ currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the $H_2O_2-stimulating$ effect on $BK_{Ca}$ currents. Using RT-PCR and western blot analysis, three subtypes of $K_{Ca}$ channels were detected in HCFs: $BK_{Ca}$ channels, small-conductance $K_{Ca}$ ($SK_{Ca}$) channels, and intermediate-conductance $K_{Ca}$ ($IK_{Ca}$) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to $H_2O_2$, but IbTX decreased $H_2O_2$-induced apoptosis. These data suggest that among the VDKCs of HCFs, $H_2O_2$ only enhances $BK_{Ca}$ currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through $BK_{Ca}$ channels.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제8권2호
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• pp.117-121
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• 2005

목 적: 로타바이러스에 의한 급성위장관염이 있는 환아들에서 AST/ALT가 증가되어 있는 경우 중 CK가 증가된 경우가 있어 이들 환아들의 임상 양상이나 검사에서 특이 소견이 있는지 확인하고자 하였다. 방 법: 2001년 1월부터 2005년 3월까지 본원에서 로타바이러스 위장관염으로 진단된 환아들 중 AST/ALT가 증가해 있고, CK가 증가해 있는 환아들의 의 무기록을 통하여 임상 양상과 검사결과를 종합하였으며, 통계학적 유의성에 대해서 조사하였다. 결 과: 총 14명의 환아가 AST나 ALT가 증가되어 있으면서 CK가 증가되어있었다. 평균 연령은 1년 5개월이었으며, 연도별 빈도는 차이가 없었다. 동반 증상으로 설사, 구토, 열, 경련, 감기 증상의 유무에 따른 차이는 없었으며, 탈수의 정도가 CK 농도 증가에 영향을 미치지 않았으며, 설사의 기간도 연관성은 없었다. 14명 모두에서 CK가 증가될 수 있는 질환의 증거는 없었으며, 회복기에 정상화되는 것을 확인하였다. AST나 ALT, LDH의 농도가 높을 수록 CK의 농도가 증가하는지 확인하였으나 연관성은 없었다. 3명의 환아에서는 CK가 1,000 IU/L이상 증가되어 있었는데, 이들에서 급성 신부전이나 경련, 근육통 등의 소견은 없었다. 결 론: 로타바이러스 위장관염 환아들에서 AST/ALT가 증가할 수 있음은 이미 알려져 있으나 그 기전은 아직 이해되지 않고 있다. 본 연구에서는 AST 나 ALT의 증가 외에도 CK가 증가될 수 있음을 확인하였으나 어떤 기전에 의하는지, CK가 증가할 수 있는 특정 조건이 있는지는 알 수 없었다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.1007-1007
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• 2005

• 대한방사선방어학회:학술대회논문집
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• 대한방사선방어학회 2010년도 춘계 학술발표회 및 심포지엄
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• pp.122-123
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• 2010

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.56.1-56.1
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• 2008

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2008년도 춘계 학술대회
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• pp.85-85
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• 2008

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2012년도 심포지엄 및 춘계학술발표회
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• pp.179-180
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• 2012

• Toxicological Research
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• 제21권4호
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• pp.291-295
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• 2005

To define the effect of silica on the stimulator of signaling pathway, we studied the phospholipase D (PLD) activity in the Rat2 fibroblasts. Silica stimulated the accumulation of labeled $[^3H]$ phosphatidylethanol$([^3H]\;PEt)$ in a time- and concentration-dependent manner. This Silicainduced PLD activity was partially attenuated by the pretreatment with U73122 (phospholipase C inhibitor), genistein (protein tyrosine kinase inhibitor), PD 98056 (MEK inhibitor) and mepacrine (phospholipase $A_2$ inhibitor). But, sphingosine (protein kinase C inhibitor) and DPI (NADPH reductase inhibitor) had not effect the PLD activity. Silica also increased the PLD activity about four fold, which imply that the PLD activity is more influenced by the mobilization of PLD than other signaling mediators. The PLD activity also partially inhibited calcium chelator EGTA or/and BAPTA/AM compared to silica. Finally, we concluded that a silica-stimulated phospholipase D activity is present in the Rat2 fibroblasts and is modulated by combination of various signaling mediators.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.55-63
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• 2001

In macrophages, lipopolysaccharide (LPS) alone or in combination with $interferon-{\gamma}\;(IFN-{\gamma})$ has been shown to release a nitric oxide (NO) through the increase of the transcription of the inducible nitric oxide synthase (iNOS) gene. To investigate the exact intracellular signaling pathway of the regulation of iNOS gene transcription by LPS plus $IFN-{\gamma},$ the effects of protein tyrosine kinase (PTK) inhibitor and protein kinase C (PKC) inhibitors on NO production, iNOS mRNA expression, nuclear $factor-_{\kappa}B\;(NF-_{\kappa}B)$ binding activity and the promoter activity of iNOS gene containing two $NF-_{\kappa}B$ sites have been examined in a mouse macrophage RAW 264.7 cells. LPS or $IFN-{\gamma}$ stimulated NO production, and their effect was enhanced synergistically by mixture of LPS and $IFN-{\gamma}.$ The PTK inhibitor such as tyrphostin reduced LPS plus $IFN-{\gamma}-induced$ NO production, iNOS mRNA expression and $NF-_{\kappa}B$ binding activity. In contrast, PKC inhibitors such as H-7, Ro-318220 and staurosporine did not show any effect on them. In addition, transfection of RAW 264.7 cells with iNOS promoter linked to a CAT reporter gene revealed that tyrphostin inhibited the iNOS promoter activity through the $NF-_{\kappa}B$ binding site, whereas PKC inhibitors did not. Taken together, these suggest that PTK, but not PKC pathway, is involved in the regulation of the iNOS gene transcription through the $NF-_{\kappa}B$ sites of iNOS promoter in RAW 264.7 macrophages by LPS plus $IFN-{\gamma}$.