• Title, Summary, Keyword: apolipoprotein

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Quantitation of Plasma Apolipoprotein A-I with a Sandwich Type Enzyme-Linked Immunosorbent Assay Using Monoclonal Antibodies

  • Lee, Min-Gyu;Kang, Jae-Seon;Jeong, Jae-Yeon;Jue, Dae-Myung;Kim, Hack-Joo
    • BMB Reports
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    • v.30 no.6
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    • pp.390-396
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    • 1997
  • A sandwich-type enzyme-linked immunosorbent assay (ELISA) for the quantification of human apolipoprotein A-I (apoA-I) was developed using monoclonal antibodies. For this assay, we used three monoclonal antibodies to trap and detect apo A-I. HDAI16 and HDA15 monoclonal antibodies were used for trapping apoA-I and HDAI8 monoclonal antibody was for detecting apoA-I. These three monoclonal antibodies were produced by immunizing mice with high density lipoprotein (HDL) isolated from human plasma. By immunoblot analysis, these three monoclonal antibodies were specific to apoA-I and showed no cross-reactivities with other plasma proteins. The results of competition assays for epitope cross-reactivity test also verified that these monoclonal antibodies identified separate and distinct epitopes on HDL and apoA-I. Affinity constants of monoclonal antibodies were measured by ELISA. Their association constants ranged from $10^7$ to $10^8$ $M^{-1}$. For this assay, pure apoA-I was isolated by affinity chromatography using monoclonal antibodies. In this sandwich assay, the amount of HRP-labeled HDAI8 bound to apoA-I trapped by HDAI16 and HDAI5 was proportional to apoA-I concentration in the range of 0 to 500ng/ml. ApoA-I concentration in plasma was calculated from the linear regression equation of standard curve. The precision and reliability of the assays are reflected in the low intra-and interassay coefficients of variation that averaged 3.25% and 4.30%, respectively. This assay is sensitive, simple, reproducible, convenient in incubation interval, and does not use radioisotope: thus it can be widely applied in clinical laboratories.

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Study on pathology of Alzheimer's disease, trends and future strategy for research (치매의 병리(病理), 연구동향(硏究動向)과 향후(向後) 연구전략(硏究戰略)에 대(對)한 고찰(考察))

  • Oh, Young-Sun;Kim, Sung-Hoon
    • Journal of Haehwa Medicine
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    • v.8 no.1
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    • pp.793-825
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    • 1999
  • For the development of drugs for alzheimer,s disease, the study was done to review the oriental pathology, clinical data, recent trends for research and strategy for future study. The results were as follows: 1. The medical term Chi-dsi implying alzheimer,s disease was referred for the first time in a medical book, Hwatasheneubijeon written by Hwa-Ta and its differentiation and treatment were studied more in Ming or Ching dynasties. Chi-dai can be differentated as weak(虛) syndrome and Shi(實) syndrome. This can be caused by deficiencies of renal Yin, renal Yang, cardiac Yin and hepatic blood, while that by deficiencies of pathological fluid(痰飮) and clotted blood(瘀血). 2. Dementia can be roughly classified as alzheimer's disease and multi-infarct disease. Its causes were known to be cholinergic transmitter, C-peptide, amyloid-${\beta}$, apolipoprotein, APP(amyloid precursor protein), TGF, MMP-9 and free radical. 3. In Korea experimental studies were chiefly done for the elimataion of C-peptide, amyloid-${\beta}$, apolipoprotein, APP for alzheimer's disease, for the development of drug inhibiting degerative change following CVA and loss of memory and also administrative measure was done by support of government. 4. Drugs of dimentia developed so far were Chi-Dai dan, extracts from aloe, mushroom, green tea, Ganoderma and also folic acid, vitamin C, DHEA and silk amino acid were reported to be effective in dimenta. 5. Future strategic research had better be done on dementia-inducing factors such as acetylcholine, C-peptide, amyloid-${\beta}$, apolipoprotein, APP, TGF, MMP-9 and free radical, development of animal model for dimentia, clinical study, epidemiology, nursing and administrative studies and also consortium for dimentia research should be formed so that repeated investment be avoided.

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Interaction of Apolipoprotein E ${\varepsilon}4$ and Education on Cognitive Decline in Korean Elders (노인의 인지감퇴에 미치는 아포지단백 E4와 교육수준의 상호작용)

  • Kim, Jae-Min;Shin, Il-Seon;Kim, Sung-Wan;Yang, Su-Jin;Park, Sang-Wook;Shin, Hee-Young;Yoon, Jin-Sang
    • Korean Journal of Biological Psychiatry
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    • v.15 no.1
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    • pp.29-34
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    • 2008
  • Objectives : This study aimed to test potential modifying effects of education on the association between apolipoprotein E ${\varepsilon}4$ (Apo E4) and cognitive decline. Methods : A community cohort(N=683) aged 65 or over completed the Korean version of Mini-Mental State Examination(MMSE-K) at baseline and two years later(1999-2001). Apo E polymorphisms were genotyped, and classified into that with or without Apo E4. Educational levels were categorized into people with or without education. Covariates included demographic(age, gender), life style(smoking, alcohol drinking), clinical (depression, sleep disorder, vascular risk factors) characteristics. Results : The association between Apo E4 and cognitive decline was significant only in the old persons with no education. The interaction term between education and Apo E4 on cognitive decline was significant(p=0.040). Conclusion : Elders with no education might be more vulnerable to the impact of Apo E4 on cognitive decline, which suggests gene-environment interaction.

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Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity

  • Yoo, Jeong-Ah;Lee, Eun-Young;Park, Ji Yoon;Lee, Seung-Taek;Ham, Sihyun;Cho, Kyung-Hyun
    • Molecules and Cells
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    • v.38 no.6
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    • pp.573-579
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    • 2015
  • Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipidbound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and $67{\AA}$ on native gel electrophoresis, while apoA-I showed scattered band pattern less than $71{\AA}$. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around $101{\AA}$ and $113{\AA}$, while apoA-I-rHDL showed almost single band around $98{\AA}$ size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, $BS_3$-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties.

Apolipoprotein E in Synaptic Plasticity and Alzheimer's Disease: Potential Cellular and Molecular Mechanisms

  • Kim, Jaekwang;Yoon, Hyejin;Basak, Jacob;Kim, Jungsu
    • Molecules and Cells
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    • v.37 no.11
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    • pp.767-776
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    • 2014
  • Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

Validation of a Newly Developed Equation for Estimating Serum Apolipoprotein B: Associations with Cardiovascular Disease Surrogate Markers in Koreans

  • Kim, Jong-Dai;Hwang, You-Cheol;Ahn, Hong-Yup;Park, Cheol-Young
    • Yonsei Medical Journal
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    • v.58 no.5
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    • pp.975-980
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    • 2017
  • Purpose: Many clinical guidelines recommend apolipoprotein B (apoB) measurement, particularly in subjects with metabolic syndrome or type 2 diabetes. Recently, we developed a new equation to estimate serum apoB (apoBE). We validated the clinical relevance of apoBE and compared the performance of the equation with conventional lipid measurements and direct measurement of apoB. Materials and Methods: Study subjects were recruited from patients who visited the Health Screening Center at Kangbuk Samsung Hospital between January and December 2009 for routine medical examinations (n=78125). For analysis of coronary calcium score, we recruited study subjects from the same institution between January 2007 and December 2010 (n=16493). Results: apoBE was significantly correlated with serum high-sensitivity C-reactive level {r=0.18 [95% confidence interval (CI), 0.18-0.19]} in partial correlation analysis adjusted for age, sex, and body mass index. apoBE was associated with a Framingham risk score indicating more than moderate risk (10-year risk ${\geq}10%$), the presence of microalbuminuria, and the presence of coronary artery calcium in multivariate logistic regression analysis. These associations were comparable to those of directly-measured serum apoB [odds ratio per 1 SD 3.02 (2.75-3.27) vs. 2.70 (2.42-3.02) for a Framingham risk score indicating more than moderate risk, 1.31 (1.21-1.41) vs. 1.35 (1.25-1.45) for the presence of microalbuminuria, and 1.33 (1.26-1.41) vs. 1.31 (1.23-1.38) for the presence of coronary calcium score respectively]. These findings were also consistently observed in subgroup analysis for subjects with type 2 diabetes. Conclusion: The associations between cardiovascular surrogate markers and apoBE were comparable to those of directly-measured apoB.

Effects of Aerobic Exercise on Serum Blood Lipids, Leptin, Ghrelin, and HOMA-IR Factors in Postmenopausal Obese Women (유산소 운동이 폐경 후 비만여성의 혈청지질, 렙틴, 그렐린 및 인슐린저항성지수에 미치는 영향)

  • Lee, Jeong-Ah;Kim, Ji-Hyeon;Kim, Jong-Won;Kim, Do-Yoen
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.2
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    • pp.549-558
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    • 2017
  • The aim of this study was to analyze the effects of aerobic exercise on the blood lipids, leptin, ghrelin, and HOMA-IR factors in obese postmenopausal Korean women. Thirty-six healthy postmenopausal women (mean age, $54.47{\pm}2.50$ years) with >32 % body fat were assigned randomly to an aerobic exercise group (n = 18) or to a "no exercise" control group (n = 18). The subjects' body composition, blood lipid, leptin, ghrelin levels, and HOMA-IR were measured before and after a 16-week line-dancing program. The exercise group showed a significant decrease in body weight, percent body fat, body mass index, visceral fat area, leptin, insulin, glucose, HOMA-IR, total cholesterol, triglycerides, apolipoprotein B, low-density lipoprotein cholesterol, and systolic and diastolic blood pressure. In addition, this group exhibited a significant increase in the apolipoprotein A-I, ghrelin, and high-density lipoprotein cholesterol levels. The energy metabolic factors that influenced the visceral fat included ghrelin, leptin, insulin, glucose, and HOMA-IR. The t-value, which determined the statistical significance of the independent variables, was significant for ghrelin, glucose, insulin, and HOMA-IR (p < 0.05). Regular and continuous aerobic exercise (e.g., line dancing) effectively improved the body composition, visceral fat, serum blood lipids, leptin, ghrelin, and HOMA-IR factors in obese postmenopausal Korean women.

The Association Between Apolipoprotein E Genotype and Lipid Profiles in Healthy Woman Workers (건강한 여성 근로자에서 Apolipoprotein E와 혈중 지질 농도와의 관련성)

  • Moon, Gi-Eun;Sung, Sook-Hee;Chang, Youn-Koun;Park, Il-Keun;Paek, Yun-Mi;Kim, Soo-Geun;Choi, Tae-In;Jin, Young-Woo
    • Journal of Preventive Medicine and Public Health
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    • v.43 no.3
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    • pp.213-221
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    • 2010
  • Objectives: Plasma lipid profiles and Apolipoprotein E (ApoE) are established risk factors for cardiovascular disease (CVD). The knowledge of lipid profile may estimate the potential victims of cardiovascular disease before its initiation and progression and offers the opportunity for primary prevention. The most common ApoE polymorphism has been found to influence plasma lipid concentrations and its correlation with CVD has been extensively investigated in the last decade. Methods: The ApoE polymorphism and its influence on plasma lipid were investigated in healthy woman workers. The information on confounding factors was obtained through a self-administered questionnaire and ApoE polymorphism was investigated using PCR. Results: The relative frequencies of alleles E2, E3 and E4 for the study population (n = 305) were 0.127, 0.750 and 0.121, respectively. ApoE polymorphism was associated with variations in plasma HDL-cholesterol lipid profile. In order to estimate the independent effects of alleles E2 and E4, as compared with E3, on lipid profile, multiple regression was performed after adjustment for confounding variables such as age, BMI, blood pressure, education status, insulin, fasting glucose, HOMA-IR, menopause. ApoE2 had a negative association with HDL cholesterol and ApoE4 had a positive association with LDL cholesterol. Conclusions: This study identified that the ApoE and CVD risk factors contribute to the lipid profiles, similar to other studies. The analysis including dietary intake and other gene in further studies may help to identify clear effects on lipid profiles as risk factor for CVD.

An Association Between Apolipoprotein E ${\varepsilon}4$ and Cognitive Function in Community-Dwelling Elders with Questionable Dementia (일 지역사회거주 치매의심 노인에서 Apolipoprotein E ${\varepsilon}4$와 인지기능 간의 연관성)

  • Moon, Seok Woo;Seo, Jeong Seok;Nam, Beom Woo;Choi, Jin Young;Lee, Chang Hoon;Park, Kyoung Un;Kim, Ki Woong
    • Korean Journal of Biological Psychiatry
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    • v.15 no.1
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    • pp.5-13
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    • 2008
  • Objectives : It was the aim of the present paper to examine the impact of the apolipoprotein E(APOE) ${\varepsilon}4$ on cognitive performance in community-dwelling elderly samples with 'questionable dementia'. Methods : Total 295 samples who were diagnosed with 'questionable dementia' in the recent year and completed the Korean version of the Consortium Establish a Registry for Alzheimer's Disease(CERAD-K) neuropsychological assessment protocol, were recruited. The CDR test established score of 0.5. Genomic DNA was extracted from the venous blood and APOE genotyping was done in this group. Their cognitive performance was compared by the occurrence of the APOE ${\varepsilon}4$ allele. Results : The impact of ${\varepsilon}4$ allele was significant in the Word List Recall Test(WLRT, F=4.511, df=1, p=0.035). The 'young-old' group aged 75 years and under had a significantly lower performance on the Word List Recall Test(WLRT, F=5.090, df=1, p=0.015), but the 'old-old' group over 75 years of age had not significantly different performance on the all the item of tests in ${\varepsilon}4$+ allele group. Conclusion : The conclusion to be drawn here is that community-dwelling elderly samples with ${\varepsilon}4$ allele in 'questionable dementia' had a significantly lower performance on the Word List Recall Test in the CERAD-K neuropsychological test batteries and the effect was prominent in the 'young-old' age group.

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Blood Lipid Levels, Nutrient Intakes and Health-Related Lifestyles of Industrial Male Workers According to Apolipoprotein E Polymorphisms (Apolipoprotein E 다형성에 따른 사업장 근로자의 혈중 지질농도, 영양소 섭취 및 건강관련 생활습관)

  • Park, Yoo-Kyoung;Cho, Sang-Woon;Kang, Ji-Yeon;Paek, Yun-Mi;Sung, Sook-Hee;Choi, Tae-In
    • Korean Journal of Community Nutrition
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    • v.13 no.5
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    • pp.713-722
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    • 2008
  • The purpose of this study was to investigate the association among nutrient intakes and health-related lifestyles with cardiovascular disease risk assessed by blood lipid profile according to Apolipoprotein E genotypes. Middle-aged industrial male workers who had completed their annual medical examination were recruited and data of 675 subjects who finished the nutrient survey were used in the analysis. Anthropometric parameters, dietary assessment (FFQ), health-related lifestyles and blood profiles were used for statistical analyses. Apo E genotype groups were classified into the following three genotypes: Apo E2 group (including E2/E2, E2/E3, E2/E4), Apo E3 group (including E3/E3), Apo E4 group (including E3/E4, E4/E4). The frequency of Apo E2, E3, and E4 allele were 13.3%, 75.0% and 11.7% respectively. There were no significant differences in the anthropometric parameters depending on different Apo E genotypes. Also, no significant differences in the nutrient intakes were found according to the genotype groups. The nutrient intakes of all subjects were similar to or higher than the level of KDRIs (Dietary Reference Intakes For Koreans) except for intakes of calcium (67.44% of KDRIs), vitamin A (73.83% of KDRIs) and vitamin $B_2$ (78.02% of KDRIs). Also, there were no significant differences of health-related lifestyles according to Apo E genotype groups. As for the lipid profiles, Apo E4 group had significantly higher total and LDL-cholesterol concentrations than the Apo E2 group (p < 0.05). We confirmed that plasma total and LDL-cholesterol concentrations were greatly influenced by Apo E genotypes. However, nutrient intakes and health-related lifestyles were not associated with Apo E genotypes.