• 제목/요약/키워드: LRP5

검색결과 25건 처리시간 0.027초

저밀도 리포단백질 수용체 관련 단백질 5(LRP5) 유전자 적중 생쥐의 개발 (Development of Low Density Lipoprotein Receptor-Related Protein 5 (LRP5) Gene Targeted Mouse)

  • 박효영;김철민;이상미;정영희;문승주;강만종
    • Reproductive and Developmental Biology
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    • 제29권1호
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    • pp.19-24
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    • 2005
  • 저밀도 리포단백질 수용체 관련 단백질 5(LRP5)는 간과 췌장을 포함하여 많은 조직에서 발현하며 아포리포단백질 E와 결합한다. 이와 같은 LRP5 유전자의 체내 기능을 규명하기 위하여 LRP5 유전자가 결손된 생쥐를 개발하였다. 먼지 LRP5 genomic DNA는 TT2 ES 세포로부터 분리하였으며 LRP5 유전자의 엑손 18에 neo 유전자를 삽입한 vector를 구축하고 TT2 ES 세포에 도입하였다. 178개의 G418 내성을 보인 세포 중 상동유전자 재조합에 의하여 targeting vector가 LRP5 유전자 위치에 삽입된 clone은 3개였다. 키메라 생쥐는 상실배기 수정을 ES 세포와 응집시켜 생산하였으며 생산된 키메라 생쥐는 C57BL/6 생쥐와 교미를 유도하여 heterozygous를 얻었다. 또한 이들 heterozygous간의 교배에 의하여 LRP5 유전자 결손 생쥐를 생산하였다. 이러한 생쥐는 LRP5 유전자의 체내 기능연구에 있어서 모델로 이용될 것으로 생각된다.

Gene Targeting of Low Density Lipoprotein(LDL) Receptor Related Protein 5(LRP5) Involved in the Wnt Signaling Pathway

  • Jeong, Young-Hee;Kim, Suck-Ho;Kim, Dong-Ho;Moon, Seung-Ju;Tokuo Yamamoto;Kang, Man-Jong
    • 한국동물번식학회:학술대회논문집
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    • 한국동물번식학회 2002년도 춘계학술발표대회 발표논문초록집
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    • pp.82-82
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    • 2002
  • The Wnt signaling pathway plays pivotal roles in embryonic development and oncogenesis through various signaling molecules inculding Frizzled receptor, recently characterized LRP5/6 and Dickkopf protein. Although Wnt signaling has been characterized in both developmental and oncogenic processes, little is known about its function in the normal adult. The ability of LRP5 to bind apolipoprotein E(apoE) and the abundant expression of LRP5 transcripts in hepatocytes, raise the possibility that LRP5 plays a role in the hepatic clearance of ApoE-containing chylomicron remonants, a major plasma lipoprotein carrying diet-derived cholesterol. (omitted)

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교차결합 실험을 통한 루신 대응 조절 단백질의 4차 구조 분석 (Analysis of quaternary structure of leucine-responsive regulatory protein (Lrp) by crosslink experiments)

  • 이의호;로버트 포쿠;로이 트엔 응구엔;이찬용
    • 미생물학회지
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    • 제53권4호
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    • pp.297-303
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    • 2017
  • 루신-대응 조절 단백질(Lrp)은 18.8 kDa의 분자량을 갖는 글로벌 조절 단백질로서 대장균과 같은 장내세균과에서 많은 대사작용 오페론의 기능적 활성도를 조절한다. 단백질의 4차 구조를 규명하기 위한 목적으로 Lrp단백질 코드하는 유전자가 삽입된 재조합 플라스미드 pQE vector를 발현시킨 6 ${\times}$ His-tag Lrp 야생형과 $^3H$로 표지된 Lrp를 분리 정제한 후 cross linker들인 glutaraldehyde, 1,2,3,4-diepoxy-butane (DEB), ethylene glycol bis (succinimidyl succinate) (EGS)으로 cross link 실험을 수행하여 Lrp가 $0.3{\mu}M$ 이하의 낮은 농도에서나 $5{\mu}M$의 높은 농도에서 이량체, 사량체, 육량체, 팔량체로 존재할 수 있음을 확인하였다.

The novel gene LRP15 is regulated by DNA methylation and confers increased efficiency of DNA repair of ultraviolet-induced DNA damage

  • Xu, Zhou-Min;Gao, Wei-Ran;Mei, Qi;Chen, Jian;Lu, Jing
    • BMB Reports
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    • 제41권3호
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    • pp.230-235
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    • 2008
  • LRP15 is a novel gene cloned from lymphocytic cells, and its function is still unknown. Bioinformatic data showed that LRP15 might be regulated by DNA methylation and had an important role in DNA repair. In this study, we investigate whether the expression of LRP15 is regulated by DNA methylation, and whether overexpression of LRP15 increases efficiency of DNA repair of UV-induced DNA damage in HeLa cells. The results showed (1) the promoter of LRP15 was hypermethylated in HeLa cells, resulting a silence of its expression. Gene expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine, but not by a histone deacetylase inhibitor, trichostatin A; (2) overexpression of LRP15 inhibited HeLa cell proliferation, and the numbers of cells in the G2/M phase of the cell cycle in cells transfected with LRP15 increased about 10% compared with controls; (3) cyclin B1 level was much lower in cells overexpressing LRP15 than in control cells; and (4) after exposure to UV radiation, the LRP15-positive cells showed shorter comet tails compared with the LRP15-negative cells. From these results we conclude that the expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to UV damage and accelerates the DNA repair rate.

High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia

  • Bhatia, Prateek;Masih, Shet;Varma, Neelam;Bansal, Deepak;Trehan, Amita
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6663-6668
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    • 2015
  • Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

Conformational Dynamics of Sclerostin-LRP6 Complex Analyzed by HDX-MS

  • Jeong, Yejing;Kim, Jinuk;Choi, Hee-Jung;Chung, Ka Young
    • Biomolecules & Therapeutics
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    • 제29권5호
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    • pp.527-535
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    • 2021
  • Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDX-MS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.

Reduced Port Surgery for Prostate Cancer is Feasible: Comparative Study of 2-port Laparoendoscopic and Conventional 5-port Laparoscopic Radical Prostatectomy

  • Akita, Hidetoshi;Nakane, Akihiro;Ando, Ryosuke;Yamada, Kenji;Kobayashi, Takahiro;Okamura, Takehiko;Kohri, Kejiro
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권11호
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    • pp.6311-6314
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    • 2013
  • Background: While 5-port laparoendoscopic radical prostatectomy is standard practice, efforts have been focused in developing a single port surgery for cosmetic reasons. However, this is still in the pioneering stage considering the challenging nature of the surgical procedures. We have therefore focused on reduced port surgery, using only 2-ports. In this study, we compared 2-port laparoendoscopic radical prostatectomy (2-port RP) and conventional 5-port laparoscopic radical prostatectomy (LRP) for clinically localized prostate carcinoma and evaluated the potential advantages of each. Materials and Methods: From January 2010 to December 2010, all 23 patients with clinically localized prostate cancer underwent LRP. Starting November, 2010, when we introduced the reduced port approach, we performed this procedure for 22 consecutive patients diagnosed with early-stage prostate cancer (cT1c, cT2N0). The patients were matched 1:1 to 2-port RP or LRP for age, preoperative serum PSA level, clinical stage, biopsy and pathological Gleason grade, surgical margin status, pad-free rates and post-operative pain. Results: There was a significant difference in operative time between the 2-port RP and LRP groups ($286.5{\pm}63.3$ and $351.8{\pm}72.4$ min: p=0.0019, without any variation in blood loss (including urine) ($945.1{\pm}479.6$ vs $1271.1{\pm}871.8ml$: p=0.13). The Foley catheter indwelling period was shorter in the 2 port RP group, but without significance ($5.6{\pm}1.8$ vs $8.0{\pm}5.6$ days: p=0.057) and the total perioperative complication rates for 2 port RP and LRP were comparable at 4.5% and 8.7% (p=0.58). There was an improvement in pad-free rates up to 6 months follow-up (p=0.090), and significantly improvement at 1 year (p=0.040). PSA recurrence was 1 (4.5%) in 2-port RP and 2 (8.7%) in LRP. Continuous epidural anesthesia was used in most of LRP patients (95.7%) and in early 2-port RP patients (40.9%). In these patients, average total amount of Diclofenac sodium was 27.8mg/patient in 2-port RP and 50.0mg/patient in LRP. Conclusions: Thus the reduced port approach is as efficacious as LRP in terms of many outcome measures, with significant cosmetic advantages and reduction in post surgical pain. This method can be readily performed safely and therefore can be recommended as a standard laparoscopic surgery for prostate cancer in the future.

Clinical Usefulness of LabChip Real-time PCR using Lab-On-a-Chip Technology for Diagnosing Malaria

  • Kim, Jeeyong;Lim, Da Hye;Mihn, Do-CiC;Nam, Jeonghun;Jang, Woong Sik;Lim, Chae Seung
    • Parasites, Hosts and Diseases
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    • 제59권1호
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    • pp.77-82
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    • 2021
  • As malaria remains a major health problem worldwide, various diagnostic tests have been developed, including microscopy-based and rapid diagnostic tests. LabChip real-time PCR (LRP) is a small and portable device used to diagnose malaria using lab-on-a-chip technology. This study aimed to evaluate the diagnostic performance of LRP for detecting malaria parasites. Two hundred thirteen patients and 150 healthy individuals were enrolled from May 2009 to October 2015. A diagnostic detectability of LRP for malaria parasites was compared to that of conventional RT-PCR. Sensitivity of LRP for Plasmodium vivax, P. falciparum, P. malariae, and P. ovale was 95.5%, 96.0%, 100%, and 100%, respectively. Specificity of LRP for P. vivax, P. falciparum, P. malariae, and P. ovale was 100%, 99.3%, 100%, and 100%, respectively. Cohen's Kappa coefficients between LRP and CFX96 for detecting P. vivax, P. falciparum, P. malariae, and P. ovale were 0.96, 0.98, 1.00, and 1.00, respectively. Significant difference was not observed between the results of LRP and conventional RT-PCR and microscopic examination. A time required to amplify DNAs using LRP and conventional RT-PCR was 27 min and 86 min, respectively. LRP amplified DNAs 2 times more fast than conventional RT-PCR due to the faster heat transfer. Therefore, LRP could be employed as a useful tool for detecting malaria parasites in clinical laboratories.

연근 및 연잎 분말을 첨가한 돈육 Patty의 품질특성 (Quality Characteristics of Pork Patty Containing Lotus Root and Leaf Powder)

  • 최영준;박현숙;박경숙;이경수;문윤희;김민주;정인철
    • 동아시아식생활학회지
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    • 제22권1호
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    • pp.33-40
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    • 2012
  • 본 연구는 연근 및 연잎분말의 첨가가 돈육 patty의 품질 특성에 미치는 영향을 검토하였다. 돈육 patty는 돈육 88%, 대두유 5%, 냉수 5%, 소금 2%를 배합하여 제조한 대조군(CTL), 여기에 연근분말 0.5% 첨가한 것(LRP), 연근분말 0.25% 및 연잎분말 0.25% 첨가한 것(LRLP), 그리고 연근분말 0.5% 첨가한 것(LLP) 등 네 종류의 돈육 patty를 제조하였다. 그리고 일반성분, 총 폴리페놀화합물 함량, 색깔, 기계적 조직감, 보수력, 가열감량, 두께 및 직경 변화, pH, VBN 함량, TBARS 및 총균수를 측정하였다. 수분함량은 CTL, 단백질 함량은 LRLP, 지방함량은 LRLP 및 LLP, 그리고 회분함량은 LRLP가 가장 높았다(p<0.05). CTL, LRP, LRLP 및 LLP의 총 폴리페놀 함량은 각각 3.34, 3.64, 3.90 및 3.90 mg/100 g이었다. 명도($L^*$)는 시료들 사이에 유의한 차이가 없었으며, 적색도($a^*$)는 CTL이 가장 높았고, 황색도는 LRLP 및 LLP가 CTL 및 LRP보다 높았다(p<0.05). 경도는 CTL 및 LRP가 LRLP 및 LLP보다 높았으며, 탄성은 LLP가 가장 낮았고, 응집성, 검성 및 저작성은 시료들 사이에 유의한 차이가 없었다. 보수력은 시료들 사이에 유의한 차이가 없었으나, 가열감량, 두께 및 직경 변화는 CTL이 가장 높았다. pH는 CTL이 가장 높았다(p<0.05). VBN 함량과 총균수는 시료들 사이에 유의한 차이가 없었다. 그리고 TBARS는 CTL이 가장 높고, LLP가 가장 낮았다(p<0.05).