• 대한의생명과학회지
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• 제14권1호
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• pp.55-58
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• 2008

Clusterin is an 80 kDa heterodimetric glycosylated protein and it plays diverse biological roles in various tissues and organs. Clusterin is reported to be associated with the pathogenesis of coronary artery disease and atherosclerosis. Therefore, we investigated the genotype for the A/G polymorphism at the position 4,183 of clusterin gene in Koreans and compared genotype of patients with control group. 100 patients (Male 63, Female 37), who previously underwent coronary artery stent due to ischemic heart disease and 100 controls (Male 36, Female 64) participated in this study. There was a significant association between 4,183 A/G polymorphism in clusterin gene and coronary artery disease (CAD). The present study shows that clusterin gene A/G polymorphism may be associated with the pathogenesis of CAD. Further studies with larger population may be needed for the development of diagnostic methods at genetic level such as DNA chip.

• 생명과학회지
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• 제20권4호
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• pp.584-588
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• 2010

Clusterin은 Apolipoprotein J 등으로도 불리우기도 하는데 이 유전자의 발현이 동맥경화의 진행에 영향을 미치며[4], 관상동맥질환과 같은 혈관질환에도 중요한 역할을 하는 것으로 보고되어 있다[9,10,18] 최근 연구결과에 따르면, clusterin 유전자 다형성 중 10580 C>A, 10613 A>G이 아프리카인에게서 HDL-C의 serum level에 영향을 미치며, 이들 변이가 African-American에게서 Caucasian보다는 드물게 나타나지만, Hispanic에게서는 빈번하게 일어나는 것으로 보고되어 있다[11]. 또 다른 연구에서는 11개의 유전자 다형성을 조사한 결과 -4453G >T, 4183 A>G, 5608 C>T 는 상관관계가 없는 것으로 나타났으나, 6316 delT 유전자 다형성은 상관관계가 있는 것으로 보고되었다[8]. 본 연구에서는 관상동맥질환 환자군과 대조군을 각각 100명으로 하여 한국인에서 clusterin 유전자 다형성을 조사하였고, 특히 -4453 T>G에서 유의한 차이를 보였다. 이는 이전의 연구결과[8]와는 다소 차이가 있는데, Miwa 등의 결과에 따르면 일본인에게서는 6316 delT가 4183 A>G 다형성보다 동맥경화와 상관관계가 크다고 보고되었으나, 본 연구결과를 분석해보면 5608 C>T 는 상관관계가 없었으며, -4453 T>G 다형성만 상관관계를 가지는 것으로 나타났다. 이러한 차이를 보이는 원인은 정확하게 지적할 수는 없으나, 다형성이 미치는 영향력이 서로 다른 유전적 그리고 환경적인 요인의 차이에 의해서 일어나는 것으로 추정된다. 따라서 본 연구결과의 의의를 확인하기 위하여서는 대상 환자 수와 대조군을 늘리고 clusterin 유전자의 여러 다형성에 대한 추가적인 연구를 할 필요가 있을 것으로 판단된다.

• Molecules and Cells
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• 제20권1호
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• pp.97-104
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• 2005

To investigate apoptosis in HC11 mammary epithelial cells, we compared the gene expression profiles of actively growing and serum-starved apoptotic cells using a mouse apoptosis gene array and $^{33}P$-labeled cDNA prepared from the RNA of the two cultures. Analysis of the arrays showed that expression of several genes such as clusterin, secreted frizzled related protein mRNA (sFRP-1), CREB-binding protein (CBP), and others was higher in the apoptotic cells whereas expression of certain genes including survivin, cell division cycle 2 homolog A (CDC2), and cyclin A was lower. These expression patterns were confirmed by RT-PCR and/or Northern analyses. We compared the expression of some of these genes in the mouse mammary gland under various physiological conditions. The expression levels of genes (clusterin, CBP, and M6P-R) up-regulated in apoptotic conditions were higher at involution than during lactation. On the other hand, genes (Pin, CDC2) downregulated in apoptotic conditions were relatively highly expressed in virgin and pregnant mice. We conclude that certain genes such as clusterin, sFRP-1, GAS1 and CBP are induced in apoptotic mammary epithelial cells, and others are repressed. Moreover, the apoptosis array is an efficient technique for comparing gene expression profiles in different states of the same cell type.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.184-189
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• 2008

The proto-oncogene protein DEK has been implicated in various human disease including cancer. We have shown that DEK induces caspase-dependent apoptosis in Drosophila by regulating histone acetylation. Reverse transcription-polymerase chain reaction (RT-PCR) method based on annealing control primers was used to screen and identify differentially expressed genes (DEGs) in DEK overexpressed HeLa cells. Among the genes identified, clusterin and fibrillarin have major role in apoptosis pathway regulation. TFIIIC and RPS24 are implicated in HAT mediated transcriptional initiation and cololectal cancer, respectively. To further analyze DEK's role in apoptosis, multiplex PCR was performed. Caspase-3, -7, and -10 and proapoptotic gene bid were newly identified as possible target genes regulated by DEK expression.

• Genomics & Informatics
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• 제3권1호
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• pp.8-14
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• 2005

Although much is known about the molecular biology of platelets, the megakaryocytes' (MKs) molecular biology was not understood so well because of their rareness. By the cloning and characterization of thrombopoietin (TPO), which is the principal regulator of the growth and development of the MKs, researches on the MKs have been growing rapidly. To understand megakaryocytopoiesis, we investigated the gene expression profile of the MKs using oligonucleotide microarray where 10,108 unique genes were spotted. Comparing the fluorescence intensities of which ratio is $\ge$ ${\mid}2{\mid}$, 372 genes were up-regulated and 541 genes were down-regulated in MKs. For confirmatory expression, RNase protection assay (RPA) establishing abundant apoptotic gene expression was carried out. In MKs, many of the known genes, including several platelet related genes, GATA binding protein were highly expressed. Particularly, TGF beta, clusterin (complement lysis inhibitor), and thymosin beta 4 (actin-sequestering molecules) were expressed highly in MKs. As MKs specific expressed genes may regulate normal and pathologic platelet (and/or MK) functions, the transcript profiling using microarray was useful on molecular understanding of MKs,

• Tuberculosis and Respiratory Diseases
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• 제63권1호
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• pp.52-58
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• 2007

연구배경: 광역학 치료는 폐암 치료에 실질적으로 이용 가능하며, 많은 연구들에서 폐암 세포에서 세포사멸을 일으킨다는 것이 이미 알려져 있다. 그러나 이 세포사멸의 기전은 아직 정확히 알려져 있지 않으며, 이에 암세포의 전사에서 초기 변화가 어떻게 일어나는 지를 알아보기 위하여 실험을 수행하였다. 방 법: 광과민성 물질인 DH-I-180-3으로 A549 세포에 처리를 하고 광역학 치료를 한 후 관찰하였다. 광역학 치료 후 DEG kit를 이용하여 폐암 세포주에서의 유전자 발현을 보았으며, 유세포 분석기를 이용하여 세포 사멸을 측정하였다. 광역학 치료 후 의미있는 변화를 보인 유전자는 염기서열분석으로 확인하였다. 결 과: 유세포분석 결과 폐암세포주는 대부분 세포괴사에 의하여 사멸되었다.광역학 치료 후, 9개의 유전자에서 명확한 변화가 있음을 발견했으며 이 중8개의 유전자를 밝혀내었다. 3-phosphoglycerate dehydrogenase와 리보솜 단백질 S29의 유전자 발현이 증가되어 있었으며, carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein, ${\beta}$-1 integrin의 유전자 발현은 감소되어 있었다. 결 론: 본 연구는 광과민성 물질인 DH-I-180-3을 이용한 광역학 치료에서 폐암 세포의 세포사멸의 주된 기전이 세포괴사에 의해 이루어 진 것임을 밝혀냈으며, 이와 관련된 유전자들 대부분이 막단백의 변화를 통해 이루어짐을 알 수 있었다.

• Molecules and Cells
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• 제37권2호
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• pp.178-186
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• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.