Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

被引：51

作者：

Mankidy, Rishikesh ^{[1
]}

Ahiahonu, Pearson W. K. ^{[1
]}

Ma, Hong ^{[1
]}

Jayasinghe, Dushmanthi ^{[1
]}

Ritchie, Shawn A. ^{[1
]}

Khan, Mohamed A. ^{[1
]}

Su-Myat, Khine K. ^{[1
]}

Wood, Paul L. ^{[1
]}

Goodenowe, Dayan B. ^{[1
]}

机构：

[1] Phenomenome Discoveries Inc & Phreedom Pharma, Saskatoon, SK S7N 4L8, Canada

来源：

LIPIDS IN HEALTH AND DISEASE | 2010年 / 9卷

关键词：

HIGH-DENSITY-LIPOPROTEIN; HMG-COA REDUCTASE; ALZHEIMERS-DISEASE; ETHANOLAMINE PLASMALOGEN; LIPID-COMPOSITION; RAT-BRAIN; DIHYDROXYACETONEPHOSPHATE ACYLTRANSFERASE; PHOSPHOLIPID-COMPOSITION; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS;

D O I：

10.1186/1476-511X-9-62

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra-and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer. Results: Using plasmalogen deficient (NRel-4) and plasmalogen sufficient (HEK293) cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA)-containing ethanolamine plasmalogen (PlsEtn) present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1) levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition. Conclusion: The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement

引用

页数：17

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