Molecular diagnosis of hypobetalipoproteinemia: An ENID review

Tarugi, Patrizia; Averna, Maurizio; Leo, Enza Di; Cefalù, Angelo Baldassare; Noto, Davide; Magnolo, Lucia; Cattin, Luigi; Bertolini, Stefano; Calandra, Sebastiano

doi:10.1016/j.atherosclerosis.2007.05.003

Cited by 162 publications

(172 citation statements)

References 49 publications

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“…Heterozigot olgularda klinik ve labarotuar bulguları normaldir. Homozigot olgularda ise bulgular infantil dönemde başlar (23) . Gastrointestinal sistem bulguları olarak klinikte steatore ve batında distansiyon ilk aylarda başlar.…”

Section: ) Düşük Ldl Nedenleriunclassified

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Hypolipodemias in children

Erdur¹,

Güzin²

2016

Buch

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ÖZPlazma lipoprotein düzeylerinin düşüklüğü ile karşımıza çıkan hipolipidemiler primer (genetik) veya sekonder (kazanılmış) nedenlere bağlı olabilir. Hiperlipidemilerin aksine, hipolipidemilerin neden ve sonuçları konularında klinisyenlerin farkındalığı çoğu zaman yeterli olmamaktadır. Bununla birlikte, hipolipidemiler altta yatan ciddi bir sorunun göstergesi olabilir. Açıklanamayan hipolipidemilerin olası nedenleri kesinlikle araştırılmalıdır. Bu makalede, çocuklarda primer ve sekonder hipolipidemilerin nedenleri ve mekanizmaları tartışılmıştır. Anahtar kelimeler: Hipolipidemi, çocuklar ABSTRACTHypolipidemia is defined as a decrease in plasma lipoprotein caused by primary (genetic) or secondary (acquired) factors. Unlike hyperlipidemia, physicians are usually inadequately aware of hypolipidemia, its causes and consequences. However, hypolipidemias can be a marker for an underlying, serious problem. Unexplained hypolipidemias should always be investigated for their possible causes. In this report, causes and mechanisms of primary and secondary hypolipidemias in children were discussed.

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Section: ) Düşük Ldl Nedenleriunclassified

“…Toplum taramalarında plazma LDL kolesterol ve apoB normalin %25-30'u kadar düşük saptanabilir. Hipokolesterolemi nedeniyle koroner kalp hastalıkları çok enderdir (23) . En önemli uyarıcı bulgu yağlı karaciğer ve transaminazlarda hafif yük-selmedir.…”

Section: B) Familyal Hipobetalipoproteinemi (Fhbl)unclassified

Hypolipodemias in children

Erdur¹,

Güzin²

2016

Buch

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“…PCSK9 affects LDLR recycling by directly binding to LDLR and increasing its degradation in the lysosome in a pH-dependent manner [3] . NH 4 Cl, a lysosome pH disruptor, abolished MG132-induced LDLR protein augmentation at 24 h, suggesting that MG132 influences LDLR degradation in the lysosome ( Figure 4A). Moreover, the disruption of endogenous PCSK9 expression by the targeted siRNA abrogated the elevation of the mature LDLR by MG132 at 24 h ( Figure 4B).…”

Section: Low Dose Of Mg132 Modestly Inhibited Proteasome Activity In mentioning

confidence: 99%

MG132, a proteasome inhibitor, enhances LDL uptake in HepG2 cells in vitro by regulating LDLR and PCSK9 expression

Yan

Gui

et al. 2014

Acta Pharmacol Sin

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Aim: Expression of liver low-density lipoprotein receptor (LDLR), a determinant regulator in cholesterol homeostasis, is tightly controlled at multiple levels. The aim of this study was to examine whether proteasome inhibition could affect LDLR expression and LDL uptake in liver cells in vitro. Methods: HepG2 cells were examined. Real-time PCR and Western blot analysis were used to determine the mRNA and protein levels, respectively. DiI-LDL uptake assay was used to quantify the LDLR function. Luciferase assay system was used to detect the activity of proprotein convertase subtilisin/kexin type 9 (PCSK9, a major protein mediating LDLR degradation) promoter. Specific siRNAs were used to verify the involvement of PCSK9. Results: Treatment of HepG2 cells with the specific proteasome inhibitor MG132 (0.03-3 μmol/L) dose-dependently increased LDLR mRNA and protein levels, as well as LDL uptake. Short-term treatment with MG132 (0.3 μmol/L, up to 8 h) significantly increased both LDLR mRNA and protein levels in HepG2 cells, which was blocked by the specific PKC inhibitors GF 109203X, Gö 6983 or staurosporine. In contrast, a longer treatment with MG132 (0.3 μmol/L, 24 h) did not change LDLR mRNA, but markedly increased LDLR protein by reducing PCSK9-mediated lysosome LDLR degradation. Furthermore, MG132 time-dependently suppressed PCSK9 expression in the HepG2 cells through a SREBP-1c related pathway. Combined treatment with MG132 (0.3 μmol/L) and pravastatin (5 μmol/L) strongly promoted LDLR expression and LDL uptake in HepG2 cells, and blocked the upregulation of PCSK9 caused by pravastatin alone. Conclusion: Inhibition of proteasome by MG132 in HepG2 cells plays dual roles in LDLR and PCSK9 expression, and exerts a beneficial effect on cholesterol homeostasis.

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“…In modern medicine, molecular diagnosis is a burgeoning field that spans from mutation analysis, 1,2 single nucleotide polymorphism (SNP) genotyping, 3 detection of chromosome abnormalities, 4,5 as well as infectious disease identification. 6 Among all the molecular a) Author to whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

An automated microfluidic system for single-stranded DNA preparation and magnetic bead-based microarray analysis

et al. 2015

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We present an integrated microfluidic device capable of performing single-stranded DNA (ssDNA) preparation and magnetic bead-based microarray analysis with a white-light detection for detecting mutations that account for hereditary hearing loss. The entire operation process, which includes loading of streptavidin-coated magnetic beads (MBs) and biotin-labeled polymerase chain reaction products, active dispersion of the MBs with DNA for binding, alkaline denaturation of DNA, dynamic hybridization of the bead-labeled ssDNA to a tag array, and white-light detection, can all be automatically accomplished in a single chamber of the microchip, which was operated on a self-contained instrument with all the necessary components for thermal control, fluidic control, and detection. Two novel mixing valves with embedded polydimethylsiloxane membranes, which can alternately generate a 3-ll pulse flow at a peak rate of around 160 mm/s, were integrated into the chip for thoroughly dispersing magnetic beads in 2 min. The binding efficiency of biotinylated oligonucleotides to beads was measured to be 80.6% of that obtained in a tube with the conventional method. To critically test the performance of this automated microsystem, we employed a commercial microarray-based detection kit for detecting nine mutation loci that account for hereditary hearing loss. The limit of detection of the microsystem was determined as 2.5 ng of input K562 standard genomic DNA using this kit. In addition, four blood samples obtained from persons with mutations were all correctly typed by our system in less than 45 min per run. The fully automated, "amplicon-in-answer-out" operation, together with the white-light detection, makes our system an excellent platform for low-cost, rapid genotyping in clinical diagnosis. V C 2015 AIP Publishing LLC.

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Molecular diagnosis of hypobetalipoproteinemia: An ENID review

Cited by 162 publications

References 49 publications

Hypolipodemias in children

Hypolipodemias in children

MG132, a proteasome inhibitor, enhances LDL uptake in HepG2 cells in vitro by regulating LDLR and PCSK9 expression

An automated microfluidic system for single-stranded DNA preparation and magnetic bead-based microarray analysis

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