• BMB Reports
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• 제31권6호
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• pp.565-571
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• 1998

The expression of the endogenous human apolipoprotein(apo)E gene was significantly induced when HepG2 cells were treated with exogenous 25-hydroxy-cholesterol. This sterol-mediated apoE gene upregulation appears to require the participation of a positive element for the apoE gene transcription (PET) ( -169/ -140), a core sequence of upstream regulatory element (URE)1 enhancer of the human apoE gene. This PET was renamed as sterol regulatory element (SRE)4 based on its new role as a sensor for the level of intracellular sterol. Furthermore, a gel mobility shift analysis showed that binding activity of the SRE4 binding protein (BP) obtained from HepG2 cells was induced by sterol treatment, while that from either MCF7 or BT20 cells remained unchanged. Binding activity of SRE4BP was also induced in mouse macrophage cells, J774A.1, by sterol treatment, but it was drastically reduced when cells were subjected to treatment of AY-9944, a potent inhibitor for sterol synthesis. However, binding activity of Spl, which is a co-binding protein to the SRE4 region, remained the same in either condition, suggesting that SRE4BP (formally known as PETBP) may be mainly responsible for the sterol-mediated regulation of the apoE gene expression. Deletion analysis of the core binding site of SRE4BP by gel mobility shift assays showed that the minimal sequence of the SRE4BP binding appears to reside between -157 and -140, confirming the identity of SRE4 with the previously determined core sequence of URE1.

• Journal of Nutrition and Health
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• 제41권5호
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• pp.402-413
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• 2008

This study was performed to investigate Apolipoprotein E phenotypes and the relationship among lipid levels, nutrient intakes, lifestyles and risk factors between subjects with and without hyperlipidemic risk. The data were collected from 675 industrial male workers who had completed annual medical examination. Compared to the normal group, the hyperlipidemic risk group in Apo E3 and E4 had significantly higher BMI (p < 0.05) and showed significantly higher body fat (%), waist circumference and WHR in all types of Apo E (p < 0.05). In addition, the hyperlipidemic risk group had significantly higher total cholesterol, LDL-cholesterol, triglyceride and AI than the normal group in all types of Apo E (p < 0.05). Intakes of protein, calcium, phosphorus, iron, vitamin A, vitamin B1, vitamin B2, vitamin C and niacin in Apo E3 were significantly lower in the hyperlipidemic risk group than in the normal group (p < 0.05). In the logistic regression analysis, after adjustment for other factors, Apo E2 + E4, waist and WHR were the significant risk factors associated with hyperlipidemia, but protein intakes were associated with significantly lower risks of hyperlipidemia (p < 0.05). In conclusion, genetic factor (Apo E2 or Apo E4), anthropometric index and nutrient intake seem to influence hyperlidemic risk. Further studies and efforts will be needed to evaluate the independent relationships among hyperlipidemic risk factors.

• 대한임상검사과학회지
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• 제36권2호
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• pp.110-114
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• 2004

Apolipoprotein E is the major lipid-carrier protein in the brain, and several studies provided evidence that apolipoprotein E(ApoE) epsilon4 allele can be considered a genetic risk factor for Alzheimer's disease(AD). Inheritance of the APOE gene has three alleles: ${\varepsilon}2$, ${\varepsilon}3$ and ${\varepsilon}4$. There are six possible genotypes: ${\varepsilon}2/{\varepsilon}2$, ${\varepsilon}3/{\varepsilon}3$, ${\varepsilon}4/{\varepsilon}4$, ${\varepsilon}2/{\varepsilon}3$, ${\varepsilon}2/{\varepsilon}4$, ${\varepsilon}3/{\varepsilon}4$. AD is characterized by a progressive loss of function and death of nerve cells in several areas of the brain. The ${\varepsilon}4$ allele is associated with a risk for developing AD. People with the ${\varepsilon}4/{\varepsilon}4$ genotype have the highest risk, but people with the ${\varepsilon}2/{\varepsilon}4$ or ${\varepsilon}3/{\varepsilon}4$ genotypes are also likely to develop the disease. 64.3% of people carry the is ${\varepsilon}3/{\varepsilon}3$ genotype, 22.1% carry the second ${\varepsilon}3/{\varepsilon}4$ genotype but, ${\varepsilon}2/{\varepsilon}2$ genotype is not usually found of people carry the 3.6% is ${\varepsilon}4/{\varepsilon}4$ genotype in a total of a test group of 140 people. The ratio of ${\varepsilon}4/{\varepsilon}4$ genotype related directly with AD is less than the ${\varepsilon}3/{\varepsilon}3$ genotype, but the ${\varepsilon}2/{\varepsilon}4$ and ${\varepsilon}3/{\varepsilon}4$ genotype ratio of indirect AD risk is 25.7% in the group of people, regardless. Thus, we have referred to the benefit from the treatment of AD through apoE genotype diagnosis.

• Molecules and Cells
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• 제37권11호
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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.

• 한국산학기술학회논문지
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• 제21권1호
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• pp.477-486
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• 2020

본 연구는 알츠하이머 치매노인을 대상으로 Apolipoprotein E (ApoE) ɛ4의 유무와 치매수준에 따른 우울과 기억력의 상관관계를 분석하고자 하였다. 임상치매척도(clinical dementia rating; CDR)가 0.5점에서 2점 사이인 65세 이상 노인 50명을 대상으로 임상치매척도, 노인용 서울언어학습검사, 레이 복합도형검사, 축약형 노인우울검사를 실시하였고 ApoE 유전자형은 구강상피세포를 채취하여 실시한 유전자 검사를 통해 확인하였다. 자료분석은 맨 휘트니 U 검정, 상관관계 분석을 실시하였다. ApoE ɛ4가 없는 경우에 CDR 1점과 2점에서 우울과 언어적 즉시회상 기억력이 유의한 음의 상관관계가 있었고(p<.05), ApoE ɛ4를 보유한 경우에는 CDR 1점에서 우울과 언어적 즉시회상, 언어적 지연회상 기억력에서 유의한 음의 상관관계가 있었다(p<.05). 우울과 언어적 즉시회상 기억력은 유의한 상관관계가 있었고 ApoE ɛ4를 보유한 경우에는 우울과 언어적 지연회상 기억력에도 유의한 상관관계가 있었다. 따라서 알츠하이머 치매의 예방 및 중재로 시각적인 훈련보다 언어적 기억력훈련이 유용할 것이며 우울치료가 상호보완적으로 도움을 줄 수 있을 것으로 기대한다.

• Molecules and Cells
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• 제38권6호
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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.

• Childhood Kidney Diseases
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• 제5권2호
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• pp.136-146
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• 2001

목 적 : 신증후군 환아의 궁극적인 예후는 양호하지만 치료시의 어려움은 빈번한 재발이다. 스테로이드에 반응을 보였던 신증후군 환아의 재발 가능성의 예측인자에 대한 여러 보고가 있었는데 최근에는 스테로이드에 반응을 보이는 신증후군 환아에서 관해기까지의 기간이 짧을수록 재발의 빈도가 의미 있게 적음이 보고되었다. 본 연구에서는 신증후군으로 처음 진단 후 스테로이드에 반응을 보였던 환아들을 대상으로 스테로이드를 사용하기 전의 고지혈증의 정도와 환아의 신기능 및 관해 유도기간과의 연관성을 검증하여, 고지혈증이 관해유도의 지연 혹은 빈발 재발 환자를 조기에 선별하여 예측지표로 사용될 수 있는지 알아보고자 시행하였다. 대상 및 방법 : 1994년 10월부터 2000넌 8월까지 본원 소아과에서 입원했던 환아들 중 처음으로 신증후군으로 진단된 후 스테로이드 치료에 반응을 보였던 33명을 대상으로 이들의 입원 및 외래 기록지를 중심으로 후향적으로 분석하였다. 결 과 : 모든 대상 환아에서 고지혈증 소견이 관찰되었으며 이중 triglyceride, total cholesterol, LDL cholesterol, apoB, Lp(a), total cholesterol/HDL cholesterol은 증가하였으나 HDL cholesteol은 증가하지 않았다. 스테로이드를 사용하기 전의 혈청 알부민은 $1.7{\pm}0.8\;g/dL$의 감소되었고 단백뇨는 $3.8{\pm}3.2\;g/24hr$로 증가보이나 크레아티닌 청소율은 $121.7{\pm}47.7\;mL/min/1.73m^2$로 감소되지 않았으며 스테로이드 사용 후 관해 유도기간은 $15.6{\pm}11.0일$이 필요했다. 혈청 알부민은 total cholesterol (r = -0.5157, P<0.005), LDL cholesterol (r = -0.5543, P<0.005), total cholesterol/HDL cholesterol (r = -0.4506, P<0.01), Lp(a) (r = -0.4570, P<0.025), apoB (r = -0.5297, P<0.025), apoB/apoAl (r = -0.5851, P<0.01), apoB/HDL cholesterol (r = -0.4961, P<0.05)등과 음의 상관관계가 있었다. 단백뇨와 크레아티닌 청소율은 스테로이드를 사용하기 전 혈청지질, 지단백과 상관관계를 보이지 않았다. 관해 유도기간은 스테로이드를 사용하기 전 HDL cholesterol (r = +0.4511, P<0.05), apoB (r = +0.5190, P<0.05), apoB/HDL cholesterol (r = +0.7169, P<0.005)과 양의 상관관계가 있었다. 결 론 : 본 연구를 통해 신증후군의 특징인 고지혈증은 서로 다른 경과의 신증후군, 서로 다른 병리조직학적 소견과 지질대사 과정에 다양한 영향을 끼치는 요인에 의해 각각의 지질 및 지단백의 상승에 차이가 있을 수 있고 이런 지질 및 지단백의 상승은 주로 간에서 생성의 증가의 발생함을 알 수 있었다. 또한 지단백중 스테로이드를 사용하기전의 HDL cholesterol, apoB, apoB/HDL cholesterol등은 관해 유도기간과 의미 있는 양의 상관관계를 보여서 신증후군 환아의 재발을 예측 할 수 있는 지표로서 임상적인 의미를 부여할 수 있을 것이다.

• Bulletin of the Korean Chemical Society
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• 제11권3호
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• pp.238-240
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• 1990

$^{31}P${$^1H$} nuclear Overhauser effects (NOEs) have been obtained for complexes formed between apolipoprotein B (apo B) and dipalmytoylphosphatidylcholine (DPPC) vesicles. NOE measurements have been conducted with broad-band irradiation of the entire $^1H$ spectrum in order to identify the proton source of the NOE. In a unilamellar vesicle formed spontaneously upon mixing aqueous suspensions of long-chain phospholipid with small amount of short-chain lecithin, the maximum NOE occurs at the N-methyl proton resonance position of the choline moiety. With addition of cholesterol to vesicles, the position of the NOE maximum shifts further away from the choline methyl frequency. For the ternary apo B-vesicle-cholesterol complex, the position of the maximum NOE lies halfway between those in vesicles with and without cholesterol.

• Journal of Nutrition and Health
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• 제31권9호
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• pp.1481-1497
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• 1998

The purpose of this study was to determine the relation between serum lipid profiles, apolipoprotein E phenotype, and dietary patterns in a cross-section of healthy individuals from Cheju-Do. Age, gender, anthropometric measurements, blood pressure, dietary consumption, drinking / smoking habits and menopausal status were surveyed. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, fasting blood glucose, and insulin levels were measured from overnight fasting blood. The study involved a total of 286 individuals(147 men and 139 women) between the ages of 20 and 60 years old. All of the subjects were recruited from a population of healthy individuals living in Cheju-Do. The results of the study are as follows : 1) Among the males, those in their 20's had the maximum food intake, while those in their 40's had the minimum food intake. For the females, food intake was the highest for those in their 30's. Energy and nutrient intakes were directly proportional to the amount of food intake. Men in their 30's were heavier than other men and women in their 40's were heavier than other women. The activity index for men in their 20's and 30's appeared to be lower than that of men above 40. The activity index of women in their 20's appeared to be lowest among all aged groups, and the index appeared to increase from the age of 30 onwards. 2) In terms of changes In serum constituents with age, men in their 40's appeared to have the highest levels of serum constituents such as lipids, glucose, and insulin. Men in their 50's showed the highest levels of serum LDL-cholesterol and glucose. Men in their 30's showed peak levels of serum triglycerides. On the other hand, women in their 50's appeared to have peak levels of serum total cholesterol, LDL-cholesterol, and triglycerides. There was no ch:ange with age in HDL-cholesterol and insulin levels for men and women. The percentage of the subjects had the following apo E phenotypes : E3/3, 91.3% ; E3/2, 5.4% ; E4/3, 2.5% ; E4/2, 0.7%. Lee's reserch with Korean female college students showed that the percentage of ApoE3/3, E3/2, E 4/2, E4/3, and E4/4 were 84.8%, 6.7%, 6.7%, 0.9%, 0.9%, respectively. The number of samples with ApoE mutation was so small that there was no statistical significance in the relation between apolipoprotein E phenotype and se겨m lipids. 3) To investigate the relati onship between weight and serum constituents, the subjects of this study were divided into three groups by BMI underweight, normal weight, and overweight. The serum constituents of men and women below the age 40 in the overweight groups belonged to the normal domain. On the other hand, serum cholesterol levels of both men and women above the age 40 in the overweight groups remained in the borderline-high region(above 200mg/dl), and the mean value of LDL-cholesterol(above 130mg/dl) and triglycerides of men were above normal. Fasting blood glucose levels also remained in the borderline-high region. Total cholesterol levels of women above the age 40 in the overweight group was in the borderline-high region. (Korean J Nutrition 31(9) : 1481-1497, 1998)

• Journal of Korean Neurosurgical Society
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• 제39권1호
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• pp.46-51
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• 2006

Objective : An Intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Atherosclerosis is one of possible mechanism, but its contribution to aneurysm formation is unclear. Human apolipoprotein E[apoE] is best known for its arterial protection from atherosclerosis. In this study we observe apoE expression in experimental cerebral aneurysms of rats to elucidate the role of apoE in the process of cerebral aneurysm formation. Methods : Twenty-four male 7-week-old Sprague-Dawley strain rats received a cerebral aneurysm induction procedure. One month[12] and three months[12] after the operation, the rats were killed, their cerebral arteries were dissected, and the regions of the bifurcation of the right anterior cerebral artery-olfactory artery [ACA-OA] bifurcations were examined histologically and immunohistochemically. Results : In the 1 month group [n=12], the ACA-OA bifurcation showed no aneurysmal change in 7 rats and early aneurysmal change in 5 rats. In the 3 months group (n=12), the bifurcation showed no aneurysmal change in 2 rats and an advanced aneurysm in 10 rats. ApoE expression were in 3 specimen in early aneurysmal change, but not in advanced aneurysms. Conclusion : ApoE expression in early aneurysmal wall suggests a possible role for apoE in early events leading to aneurysm formation. Further studios are necessary to elucidate the exact role of apoE in the pathophysiology of cerebral aneurysm.