Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S]
During atherogenesis, the extracellular pH of atherosclerotic lesions decreases. Here, we examined the effect of low, but physiologically plausible pH on aggregation of modified LDL, one of the key processes in atherogenesis. LDL was treated with SMase, and aggregation of the SMase-treated LDL was f...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2012-09-01
|
Series: | Journal of Lipid Research |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520418279 |
id |
doaj-f42ffa52780345e49334df24c906d1ab |
---|---|
record_format |
Article |
spelling |
doaj-f42ffa52780345e49334df24c906d1ab2021-04-28T06:05:19ZengElsevierJournal of Lipid Research0022-22752012-09-0153918321839Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S]Mia Sneck0Su Duy Nguyen1Tero Pihlajamaa2Gebrenegus Yohannes3Marja-Liisa Riekkola4Ross Milne5Petri T. Kovanen6Katariina Öörni7Wihuri Research Institute, Helsinki, Finland; To whom correspondence should be addressed. e-mail: kati.oorni@wri.fi.Wihuri Research Institute, Helsinki, FinlandProgram in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Helsinki, FinlandLaboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, Helsinki, FinlandLaboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, Helsinki, FinlandLipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, CanadaWihuri Research Institute, Helsinki, Finland; To whom correspondence should be addressed. e-mail: kati.oorni@wri.fi.To whom correspondence should be addressed. e-mail: kati.oorni@wri.fi.; Wihuri Research Institute, Helsinki, FinlandDuring atherogenesis, the extracellular pH of atherosclerotic lesions decreases. Here, we examined the effect of low, but physiologically plausible pH on aggregation of modified LDL, one of the key processes in atherogenesis. LDL was treated with SMase, and aggregation of the SMase-treated LDL was followed at pH 5.5–7.5. The lower the pH, the more extensive was the aggregation of identically prelipolyzed LDL particles. At pH 5.5–6.0, the aggregates were much larger (size >1 µm) than those formed at neutral pH (100–200 nm). SMase treatment was found to lead to a dramatic decrease in α-helix and concomitant increase in β-sheet structures of apoB-100. Particle aggregation was caused by interactions between newly exposed segments of apoB-100. LDL-derived lipid microemulsions lacking apoB-100 failed to form large aggregates. SMase-induced LDL aggregation could be blocked by lowering the incubation temperature to 15°C, which also inhibited the changes in the conformation of apoB-100, by proteolytic degradation of apoB-100 after SMase-treatment, and by HDL particles. Taken together, sphingomyelin hydrolysis induces exposure of protease-sensitive sites of apoB-100, whose interactions govern subsequent particle aggregation. The supersized LDL aggregates may contribute to the retention of LDL lipids in acidic areas of atherosclerosis-susceptible sites in the arterial intima.http://www.sciencedirect.com/science/article/pii/S0022227520418279sphingomyelinaseaggregationatherosclerosisapolipoproteinlow density lipoprotein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mia Sneck Su Duy Nguyen Tero Pihlajamaa Gebrenegus Yohannes Marja-Liisa Riekkola Ross Milne Petri T. Kovanen Katariina Öörni |
spellingShingle |
Mia Sneck Su Duy Nguyen Tero Pihlajamaa Gebrenegus Yohannes Marja-Liisa Riekkola Ross Milne Petri T. Kovanen Katariina Öörni Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S] Journal of Lipid Research sphingomyelinase aggregation atherosclerosis apolipoprotein low density lipoprotein |
author_facet |
Mia Sneck Su Duy Nguyen Tero Pihlajamaa Gebrenegus Yohannes Marja-Liisa Riekkola Ross Milne Petri T. Kovanen Katariina Öörni |
author_sort |
Mia Sneck |
title |
Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S] |
title_short |
Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S] |
title_full |
Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S] |
title_fullStr |
Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S] |
title_full_unstemmed |
Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH[S] |
title_sort |
conformational changes of apob-100 in smase-modified ldl mediate formation of large aggregates at acidic ph[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2012-09-01 |
description |
During atherogenesis, the extracellular pH of atherosclerotic lesions decreases. Here, we examined the effect of low, but physiologically plausible pH on aggregation of modified LDL, one of the key processes in atherogenesis. LDL was treated with SMase, and aggregation of the SMase-treated LDL was followed at pH 5.5–7.5. The lower the pH, the more extensive was the aggregation of identically prelipolyzed LDL particles. At pH 5.5–6.0, the aggregates were much larger (size >1 µm) than those formed at neutral pH (100–200 nm). SMase treatment was found to lead to a dramatic decrease in α-helix and concomitant increase in β-sheet structures of apoB-100. Particle aggregation was caused by interactions between newly exposed segments of apoB-100. LDL-derived lipid microemulsions lacking apoB-100 failed to form large aggregates. SMase-induced LDL aggregation could be blocked by lowering the incubation temperature to 15°C, which also inhibited the changes in the conformation of apoB-100, by proteolytic degradation of apoB-100 after SMase-treatment, and by HDL particles. Taken together, sphingomyelin hydrolysis induces exposure of protease-sensitive sites of apoB-100, whose interactions govern subsequent particle aggregation. The supersized LDL aggregates may contribute to the retention of LDL lipids in acidic areas of atherosclerosis-susceptible sites in the arterial intima. |
topic |
sphingomyelinase aggregation atherosclerosis apolipoprotein low density lipoprotein |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520418279 |
work_keys_str_mv |
AT miasneck conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT suduynguyen conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT teropihlajamaa conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT gebrenegusyohannes conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT marjaliisariekkola conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT rossmilne conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT petritkovanen conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs AT katariinaoorni conformationalchangesofapob100insmasemodifiedldlmediateformationoflargeaggregatesatacidicphs |
_version_ |
1721504234358177792 |