• Natural Product Sciences
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• 제19권4호
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• pp.360-365
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• 2013

Baicalin has antioxidant, anti-inflammatory and anti-diabetic properties. IL-6 is a primary proinflammatory cytokine that contributes to impaired insulin signaling in liver. This study was carried out to investigate whether baicalin improves IL-6-mediated insulin resistance in liver. Hepa-1c1c7 cells were pre-treated with 50 and 100 ${\mu}M$ baicalin in complete media for 1 h and then cultured in the presence or absence of IL-6 (20 ng/ml). These results demonstrated that baicalin restored IL-6-suppressed expression of insulin receptor substrate (IRS)-1 protein, downregulated IL-6-increased gene expression of C-reactive protein (CRP) and suppressor of cytokine signaling (SOCS)-3, and inhibited LPS-induced production of IL-6 in Hepa-1c1c7 cells. These findings indicate that baicalin may ameliorate hepatic insulin resistance via improvement of IL-6-mediated impaired insulin signaling in hepatocytes.

• 약학회지
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• 제39권6호
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• pp.689-694
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• 1995

Sphingolipids play important roles in cell regulation and signal transduction. Recently, a sphinogomyelin cycle has been described in which activation of neutral sphingomyelinase leads to the breakdown of sphingomyelin and the generation of ceramide. Ceramide, in turn, has emerged as a candidate intracellular mediator for the action of certain cell agonists and has multiple biologic actions. Ceramide is a potent suppressor of cell growth and an inducer of apoptosis. The present studies show that exposure of IM-9 cells to ceramide resulted in internucleosomal cleavage of DNA, yielding laddered patterns of oligonucleosomal fragments characteristic of apoptosis. DNA fragmentation induced by ceramide was also confirmed by diphenylamine assay. The effect of ceramide on cell cycle progression was also studied. The addition of ceramide increase G$_{1}$ phase distribution in cell cycle. Cell cycle-related cyclin D$_{1}$ gene expression was decreased in a time-dependent manner. These results suggest that apoptosis induced by ceramide is related to cell cycle associated with the alteration of cell cycle in IM-9 cells.

• International Journal of Industrial Entomology and Biomaterials
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• 제12권2호
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• pp.57-61
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• 2006

Suppressor of cytokine signaling (SOCS) is known to be as a negative feedback regulator in Janus kinase signal transducer and activator of transcription signaling. Highly conserved SOCS box domain was cloned from a Korean malaria vector, Anopheles sinensis. Sequence analysis indicates that it has identity to Anopheles gambiae (96%), Aedes aegypti (94%), Drosophila melanogaster (78%), Mus musculus (72%) and Homo sapiens (72%), respectively. Tissue specificity RT-PCR demonstrated that the expression level of AsSOCS transcript was high at abdomen, midgut, and ovary, whereas developmental expression patterns showed that the level of AsSOCS was high at egg, early pupae, and adult female. On the other hand, RT-PCR analysis after bacterial challenge showed that SOCS mRNA was strongly induced in larvae. In addition, it was also induced by various immune elicitors such as lipoteicoic acid, CpG-DNA, and laminarin. It seems that AsSOCS, repressor of JAK-STAT pathway, is highly conserved in mosquito, and may play an important role in mosquito innate immune response.

• International Journal of Industrial Entomology and Biomaterials
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• 제12권2호
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• pp.63-67
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• 2006

Suppressor of cytokine signaling (SOCS) is known to playa key role as a negative feedback regulator in JAK/STAT signaling cascade in innate immunity. Our laboratory has recently been interested in elucidating the interactions between Spodoptera exigua (Se) and SeNPV. This context leads us to clone and characterize SeSOCS that may have important functions in response to SeNPV infection. Using the RT-PCR and TA cloning approach, we found a partial fragment (416 bp) of SeSOCS. Blast search and multiple alignment data showed that it has a homology to various insects such as Anopheles gambiae (78%), Aedes aegypti (75%), Drosophila melanogastar (77%), Mus musculus (69%), and Homo sapiens (69%). Temporal induction patterns of SeSOCS were analysed after being immune-challenged with either NPV or laminarin. It showed that the level of SeSOCS mRNA was strongly induced in a biphasic manner in response to SeNPV and laminarin, respectively. It seems that SOCS, a negative regulator of JAK/STAT signaling system is also present in S. exigua and may playa role in innate immunity albeit its precise role should be further elucidated at the molecular and cellular level in the early phase of SeNPV infection in larvae.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3719-3724
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• 2013

Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Results: Nineteen studies involving 2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04-26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4 (95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysis gave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1A methylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32-2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender, pathology, TNM stage and smoking behavior among NSCLC cases. Conclusion: This meta-analysis suggests a significant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumor suppressor gene. Large-scale and well-designed case-control studies are needed to validate the associations identified in the present meta-analysis.

• BMB Reports
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• 제43권2호
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• pp.97-102
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• 2010

Clenbuterol, a $\beta_2$-adrenoceptor agonist, has been proven to be a powerful repartition agent that can decrease fat deposition. Based on results from our previous cDNA microarray experiment of pig clenbuterol administration, a novel up-regulated EST was full-length cloned (4859 bp encoding 1041 amino acids) and found to be the pig homolog of large tumor suppressor 2 (Lats2). We mapped pig Lats2 to chromosome 11p13-14 by using FISH, and western blotting demonstrated that pig Lats2 protein was most abundant in adipose. In Drosophila, Lats2 ortholog was reported as a key component of the Hippo pathway which regulates cell differentiation and growth. Here, we show that pig Lats2 exhibit inverted expression to YAP1, another member of the Hippo pathway which positively regulates cell growth and proliferation, during the differentiation of 3T3-L1 preadipocytes. Our results suggested that Lats2 may involve in Hippo pathway regulating the fat reduction by inhibiting adipocyte differentiation and growth.

• 대한골관절종양학회지
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• 제9권1호
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• pp.77-83
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• 2003

공격성 섬유종증은 비교적 드문 연부 조직 종양이지만, 국소 증식 및 침윤성이 강한 종양으로 알려져 있다. 그렇지만 종양 증식에 관한 정확한 기전은 아직 보고되어 지지 않고 있다. 한편, 종양 억제 유전자 PTEN은 국소 침윤성과 전이를 보이는 여러 암 조직에서 발현의 감소 또는 돌연 변이가 보고되고 있다. 본 연구에서는 공격성 섬유종증에서 면역조직화학적 염색과 면역탁본법을 통해 종양 억제 유전자 PTEN의 발현의 양상을 알아보고자 하였다. 면역 탁본법과 면역조직화학적 염색상 PTEN의 발현은 정상 근막 조직에서는 균일하게 발현되었으나, 공격성 섬유종증 종양조직에서는 발현이 감소하였다. 공격성 섬유종증에서 PTEN발현의 감소는 급속한 증식과 재발 및 주위 조직의 침윤이 특징인 공격성 섬유종증의 병인에 관련이 있을 것으로 사료된다.

• 대한의생명과학회지
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• 제19권1호
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• pp.1-8
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• 2013

Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-${\alpha}$-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. MMP-3 is a zinc-dependent protease recently reported to activate intracellular apoptotic signaling. In this study we examined the regulation of MMP-3 expression by parkin in TNF-${\alpha}$-treated HeLa cells. Furthermore, we investigated the signaling pathway involved in parkin-induced expression of MMP-3. We found that HeLa cells exhibit low levels of MMP-3 but is induced after introduction of the parkin gene into HeLa cells. Furthermore, MMP-3 expression increased further when parkin expressing cells were treated with TNF-${\alpha}$. Using chemical inhibitors of cell signaling pathways, we found that MEK-1 (PD98059), PI3K (LY294002), p38 MAPK (SB203580), and JNK inhibitors alleviated parkin-induced up-regulation of MMP-3. Finally, we show that TNF-${\alpha}$-induced cell death in parkin expressing cells is inhibited by using a MMP-3 inhibitor. These results suggest that parkin expression induces prolonged expression of MMP-3 via MEK-1, PI3K, MAPK, and JNK pathway in HeLa cells allowing the HeLa cells to become sensitive to TNF-${\alpha}$-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-${\alpha}$ treated HeLa cells.

• The Plant Pathology Journal
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• 제30권1호
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• pp.58-67
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• 2014

The multifunctional triple gene block protein 1 (TGB1) of the Potexvirus Alternanthera mosaic virus (AltMV) has been reported to have silencing suppressor, cell-to-cell movement, and helicase functions. Yeast two hybrid screening using an Arabidopsis thaliana cDNA library with TGB1 as bait, and co-purification with TGB1 inclusion bodies identified several host proteins which interact with AltMV TGB1. Host protein interactions with TGB1 were confirmed by biomolecular fluorescence complementation, which showed positive TGB1 interaction with mitochondrial ATP synthase delta' chain subunit (ATP synthase delta'), light harvesting chlorophyll-protein complex I subunit A4 (LHCA4), chlorophyll a/b binding protein 1 (LHB1B2), chloroplast-localized IscA-like protein (ATCPISCA), and chloroplast ${\beta}$-ATPase. However, chloroplast ${\beta}$-ATPase interacts only with $TGB1_{L88}$, and not with weak silencing suppressor $TGB1_{L88}$. This selective interaction indicates that chloroplast ${\beta}$-ATPase is not required for AltMV movement and replication; however, TRV silencing of chloroplast ${\beta}$-ATPase in Nicotiana benthamiana induced severe tissue necrosis when plants were infected by AltMV $TGB1_{L88}$ but not AltMV $TGB1_{L88}$, suggesting that ${\beta}$-ATPase selectively responded to $TGB1_{L88}$ to induce defense responses.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4937-4944
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• 2015

MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E-BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p-4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC.