• 제목/요약/키워드: degradation pathway

검색결과 432건 처리시간 0.025초

Effect of nitric oxide on the expression of matrix metalloproteinases by the UV irradiated human dermal fibroblasts

  • Taeboo Choe;Lee, Bumchun;Park, Inchul;Seokil Hong
    • 대한화장품학회지
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    • 제28권1호
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    • pp.31-41
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    • 2002
  • The production of matrix matalloproteinases(MMPs) by the UV irradiated skin fibroblast and the degradation of extracellular matrix(ECM) by these enzymes is known as one of the main reasons of photoaging. Recently, Fisher group showed that the MMP expression is mainly regulated by the mitogen-activated protein(MAP) kinas family, such as extracellular signal-regulated kinase(ERK), c-Jun amino-terminal kinase(JNK) and p38, each of which forms a signaling pathway. In this work we first examined the effect of nitric oxide (NO) on the production of MMP-1 and MMP-2 by the human dermal fibroblasts (HDFs). NO is a multifunctional messenger molecule generated from L-arginine and involved in many kinds of signaling pathway. We found that the treatment of HDF with NO donor, sodium nitroprusside (SNP) enhanced the expression of MMPs with or without UV irradiation and the treatment with nitric oxide synthase (NOS) inhibitors resulted in the significant decrease of MMPs production. From these results, we concluded that the production of MMPs by the UV irradiated HDF is regulated through the signaling pathway involving NO and cyclic GMP.

BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway

  • Jiang, Lan;Yang, Qianhong;Gao, Jianjun;Yang, Jiahong;He, Jiaqi;Xin, Hong;Zhang, Xuemei
    • Molecules and Cells
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    • 제44권8호
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    • pp.557-568
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    • 2021
  • Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we further investigated the role of BK channels in bone development and explored whether BK channels impacted the differentiation and proliferation of osteoblasts via the canonical Wnt signaling pathway. Our findings demonstrated that knockout of Kcnma1 disrupted the osteogenesis of osteoblasts and inhibited the stabilization of β-catenin. Western blot analysis showed that the protein levels of Axin1 and USP7 increased when Kcnma1 was deficient. Together, this study confirmed that BK ablation decreased bone mass via the Wnt/β-catenin signaling pathway. Our findings also showed that USP7 might have the ability to stabilize the activity of Axin1, which would increase the degradation of β-catenin in osteoblasts.

Meclofenamate Suppresses MUC5AC Mucin Gene Expression by Regulating the NF-kB Signaling Pathway in Human Pulmonary Mucoepidermoid NCI-H292 Cells

  • Jiho Ryu;Kyung-il Kim;Rajib Hossain;Misoon Lee;Jin Tae Hong;Hyun Jae Lee;Choong Jae Lee
    • Biomolecules & Therapeutics
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    • 제31권3호
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    • pp.306-311
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    • 2023
  • The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.

BAG5 regulates PTEN stability in MCF-7 cell line

  • Zhang, Ying;Gao, Haiyan;Gao, Haidong
    • BMB Reports
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    • 제46권10호
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    • pp.490-494
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    • 2013
  • The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor-suppressing lipid phosphatase that is frequently absent in breast tumors. Thus, the stability of PTEN is essential for tumor prevention and therapy. The ubiquitin-proteasome pathway has an important role in regulating the functions of PTEN. Specifically, carboxyl terminus Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase of PTEN, can regulate PTEN levels. In this study, we report that BCL-2-associated athanogene 5 (BAG5), a known inhibitor of CHIP activity, reduces the degradation of PTEN and maintains its levels via an ubiquitylation-dependent pathway. BAG5 is identified as an antagonist of cell tumorigenicity.

ESCRT, autophagy, and frontotemporal dementia

  • Lee, Jin-A;Gao, Fen-Biao
    • BMB Reports
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    • 제41권12호
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    • pp.827-832
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    • 2008
  • Many age-dependent neurodegenerative diseases are associated with the accumulation of abnormally folded proteins within neurons. One of the major proteolytic pathways in the cell is the autophagy pathway, which targets cytoplasmic contents and organelles to the lysosomes for bulk degradation under various physiological and stressful conditions. Although the importance of autophagy in cellular physiology is well appreciated, its precise roles in neurodegeneration remain largely unclear. Recent studies indicate that components of the endosomal sorting complex required for transport (ESCRT) are important in the autophagy pathway. Reduced activity of some ESCRT subunits leads to the accumulation of autophagosomes and failure to clear intracellular protein aggregates. Interestingly, rare mutations in CHMP2B, an ESCRT-III subunit, are associated with frontotemporal dementia linked to chromosome 3 (FTD3). Mutant CHMP2B proteins seem to disrupt the fusion of autophagosomes and lysosomes in cell culture models. These findings suggest a potential mechanism for the pathogenesis of FTD3 and possibly other neurodegenerative diseases as well.

Involvement of IKK/IkBα/NF-kB p65 Signaling into the Regulative Effect of Engeletin on MUC5AC Mucin Gene Expression in Human Airway Epithelial Cells

  • Hossain, Rajib;Kim, Kyung-il;Li, Xin;Lee, Hyun Jae;Lee, Choong Jae
    • Biomolecules & Therapeutics
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    • 제30권5호
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    • pp.473-478
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    • 2022
  • In this study, we examined whether engeletin exerts an effect on the gene expression of MUC5AC mucin, in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with engeletin for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of engeletin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Engeletin suppressed the mRNA expression and production of MUC5AC mucin, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest engeletin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

대식세포주에서 인슐린이 $I{\kappa}B/NF-{\kappa}B$ 경로 활성화에 미치는 영향 (Role of Insulin in the Activation of $NF-{\kappa}B/I{\kappa}B$ Pathway in Macrophage Cells)

  • 이상민;장연실;이춘택;김영환;한성구;심영수;유철규
    • Tuberculosis and Respiratory Diseases
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    • 제68권3호
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    • pp.168-174
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    • 2010
  • Background: Sepsis still has a high mortality rate despite adequate supportive care. Newer therapeutic modalities have been developed but they have generally ended in failure. Recently, insulin was reported to have an anti-inflammatory effect by inhibiting the $I{\kappa}B/NF-{\kappa}B$ pathway, and may have therapeutic potential in sepsis. However, the precise mechanism of the anti-inflammatory effect of insulin is unclear. This study examined the role of insulin in activating $I{\kappa}B/NF-{\kappa}B$ in macrophage. Methods: Raw 264.7 cells, a murine macrophage cell line, were used in this experiment. Western blotting using $I{\kappa}B$ Ab and phosphor-specific $I{\kappa}B$ Ab was performed to evaluate the degradation and phosphorylation of $I{\kappa}B$ cells. For the $I{\kappa}B$ Kinase (IKK) activity, an immune complex kinase assay was performed. The level of interleukin-6 (IL-6) was measured by ELISA to determine the level of proinflammatory cytokine. Results: $I{\kappa}B{\alpha}$ degradation began 30 min after lipopolysaccharide (LPS) treatment. However, an insulin pretreatment suppressed the $I{\kappa}B{\alpha}$ degradation caused by the LPS treatment. The phosphorylation of $I{\kappa}B{\alpha}$ and IKK activity was also inhibited by the insulin pretreatment. Finally, the insulin pretreatment showed a tendency to suppress the induction of IL-6 by LPS. Conclusion: Insulin might have an anti-inflammatory effect though partial inhibition of the $I{\kappa}B/NF{\kappa}B$ pathway in macrophage cell lines.

Arthrobacter sp. Strain KU001 Isolated from a Thai Soil Degrades Atrazine in the Presence of Inorganic Nitrogen Sources

  • Sajjaphan, Kannika;Heepngoen, Pimpak;Sadowsky, Michael J.;Boonkerd, Nantakorn
    • Journal of Microbiology and Biotechnology
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    • 제20권3호
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    • pp.602-608
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    • 2010
  • An atrazine-degrading bacterium, strain KU001, was obtained from a sugarcane field at the Cane and Sugar Research and Development Center at the Kasetsart University, Kamphaeng Saen Campus, Thailand. Strain KU001 had a rod-to-coccus morphological cycle during growth. Biolog carbon source analysis indicated that the isolated bacterium was Arthrobacter histidinolovorans. Sequence analysis of the PCR product indicated that the 16S rRNA gene in strain KU001 was 99% identical to the same region in Arthrobacter sp. The atrazine degradation pathway in strain KU001 consisted of the catabolic genes trzN, atzB, and atzC. Strain KU001 was able to use atrazine as a sole nitrogen source for growth, and surprisingly, atrazine degradation was not inhibited in cells grown on ammonium, nitrate, or urea, as compared with cells cultivated on growth-limiting nitrogen sources. During the atrazine degradation process, the supplementation of nitrate completely inhibited atrazine degradation activity in strain KU001, whereas ammonium and urea had no effect on atrazine degradation activity. The addition of strain KU001 to sterile or nonsterile soils resulted in the disappearance of atrazine at a rate that was 4- to 5-fold more than that achieved by the indigenous microbial community. The addition of citrate to soils resulted in enhanced atrazine degradation, where 80% of atrazine disappeared within one day following nutrient supplementation.

토양중 [$^{14}C$Carbofuran의 분해 및 비추출성 잔류분의 특성 (Degradation of [$^{14}C$]Carbofuran in Soils and Characterization of its Nonextractable Residues)

  • 박창규;이영득
    • Applied Biological Chemistry
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    • 제38권3호
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    • pp.263-268
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    • 1995
  • 침투성 살충제의 일종인 carbofuran을 대상으로 수분조건을 달리한 논과 밭상태의 토양중 분해경로상 차이점과 비추출성 잔류분의 특성을 비교, 검토하였다. 침수 및 습윤상태로 수분조건을 조절한 토양에 [$3-^{14}C$]Carbofuran을 정상적 포장살포약량인 1.0mg/kg (87.8kBq/50g 토양)수준으로 처리하고 경시적으로 특성별 방사능과 분해산물의 분포를 조사하였다. 토양중 carbofuran의 초기분해경로는 수분조건에 따라 차이를 보여 침수상태에서는 가수분해가 우세하였던 반면 습윤상태에서는 산화가 주된 초기분해반응으로 나타났다. 또한 분해속도에 있어서도 토양중 반감기가 각각 34일 및 50일로 수분조건에 따라 차이를 보였다. 토양중에 처리한 carbofuran 및 분해산물중 상당량이 비추출성으로 전환, 처리 60일후 $24{\sim}39%$에 달하였으며 주로 토양유기물에 분포하였다. 비추출성 방사능의 토양유기물중 분포를 조사한 결과 처리후 시간이 경과함에 따라 carbofuran 및 그 분해산물들은 fulvic acid, humic acid 및 humin분획에 혼입되었으며 겔여과크로마토그래피에 의하여 분자량 $10^4$ 이상의 혼입고분자화합물이 존재함을 밝혔다.

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미생물에 의한 cholesterol과 그유도체의 분해기구 II 19-Hydronyandrost-4-ene-3, 17-dione의 분리 (Degradation Mechanism of Cholesterol and Its Derivatives by Microorganisms. II Iso of-Hydronyandrost-4-ene-3,17-dione)

  • 이상섭
    • 약학회지
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    • 제12권3_4호
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    • pp.76-84
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    • 1968
  • When 19-hydroxycholesterol acetate was added into CSD-10 in Nutrient Broth or in a mineral salts medium consisting of KH$_{2}$PO$_{4}$(0.1%), $K_{2}$HPO$_{4}$(0.1%), NH$_{4}$NO$_{3}$(0.1%), MgSO$_{4}$(0.02%), CaCl$_{2}$(0.002%), and FeCl$_{3}$(0.005%), a substantial amount of 19-hydroxyandrost-4-ene-3,17-dione was accumulated prior to accumulation of estrone. From this result and all of previous works, a tentative degradation pathway of 19-hydroxycholesterol acetate to estrone by CSD-10 was derived. 19-hydroxyandrost-4-ene-3,17-dione seems to be an attractive intermediate for the synthesis of 19-norsteroids.

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