• BMB Reports
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• v.31 no.6
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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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• v.41 no.5
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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.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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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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• 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.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.1
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• pp.477-486
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• 2020

This study was undertaken to analyze the correlation between depression and memory, by considering the occurrence of ApoE ɛ4 and clinical dementia rating in the elderly with Alzheimer's dementia. This study included 50 participants over 65 years of age, evaluated with CDR 0.5 to 2. We performed CDR, SVLT-E, RCFT, SGDS-K, and ApoE genotyping. Spearman's correlation analysis was used for determining the correlation between depression and memory. The results indicate a significant negative correlation between depression and immediate recall verbal memory in the CDR 1 and 2 without ApoE ɛ4 carrier group (p<0.05). Furthermore, a significant negative correlation was also determined between depression and delayed recall verbal memory in the CDR 1 of the same group. Ed. Notes: The previous sentence already shows this correlation. I suggest this should be deleted from this statement. However, no significant correlation was observed between depression and visual memory. This study found a significant correlation between depression and immediate recall verbal memory. Also, the presence of ApoE ɛ4 indicates a significant correlation between depression and delayed verbal recall memory. Taken together, our results indicate that verbal memory training rather than visual memory training can be more effective in early AD. Also, the treatment of depression will provide a complementary effect.

• 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.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.136-146
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• 2001

Purpose : One of the most difficult problems in the care of children with nephrotic syndrome remains the occurrence of relapses, despite initial response to steroids. Constantinescu reported that rapidity of initial response to steroid therapy could predict fewer relapses in the first year. So we evaluated the changes in serum lipid abnormalities in children with corticosensitive nephrotic syndrome before steroid treatment and the correlation between serum lipid levels and renal function, days to remission. Methods . We analyzed the Medical records of children who were managed by us between October 1994 and August 2000. In 33 patients with corticosensitive nephrotic syndrome, we evaluated the correlation between serum lipid levels and renal function [Creatinine clearance(Ccr)] and proteinuria before steroid treatment, and days to remission defined as the third day when the patient's urine becomes protein free. Results : There were 21 males and 12 females. Median age at presentation was 6.4 years (range: 1.8-17.3 years). Median days to remission were 15.4 days (range 4-42 days) on Prednisolone $60mg/m^2$ daily. The increased levels of triglyceride, total cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol/HDL cholesterol, Lipoprotein(a) were observed. But the level of HDL cholesterol was not increased. Serum albumin was decreased a]id proteinuria was increased before steroid treatment. But Ccr was not decreased. There were negative correlation between serum albumin and 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), lipoprotein(a) (r = -0.4570, P<0.025), apolipoprotein B (r = -0.5297, P<0.025), apolipoprotein B/apolipoprotein Al (r = -0.5851, P<0.01), apolipoprotein B/HDL cholesterol (r = -0.4961, P<0.05) before steroid treatment. There was no correlation between proteinuria and serum lipid profiles. Also Ccr and serum lipid profiles were not correlated. There was positive correlation between days to remission and HDL cholesterol (r = +0.4511, P<0.05), apolipoprotein B (r = +0.5190, P<0.05), apolipoprotein B/HDL cholesterol (r = +0.7169, P<0.005). Conclusions : This results reveal that HDL cholesterol, apolipoprotein B and apolipoprotein B/HDL cholesterol can be used as a predictive factor in corticosensitive nephrotic syndrome. We could not determine the significant level of these lipids for insufficient patients number, but these level may predict future relapses of corticosensitive nephrotic syndrome patients and thus may allow to better management and treatment protocols. More data and long term follow up studies should be needed. (J Korean Soc Pediatr Nephrol 2001;5 : 136-46)

• Bulletin of the Korean Chemical Society
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• v.11 no.3
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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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• v.31 no.9
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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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• v.39 no.1
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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.