Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase
LDL particles that enter the arterial intima become exposed to proteolytic and lipolytic modifications. The extracellular hydrolases potentially involved in LDL modification include proteolytic enzymes, such as chymase, cathepsin S, and plasmin, and phospholipolytic enzymes, such as secretory phosph...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-07-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520371029 |
| _version_ | 1818386851320299520 |
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| author | Riia Plihtari Eva Hurt-Camejo Katariina Öörni Petri T. Kovanen |
| author_facet | Riia Plihtari Eva Hurt-Camejo Katariina Öörni Petri T. Kovanen |
| author_sort | Riia Plihtari |
| collection | DOAJ |
| description | LDL particles that enter the arterial intima become exposed to proteolytic and lipolytic modifications. The extracellular hydrolases potentially involved in LDL modification include proteolytic enzymes, such as chymase, cathepsin S, and plasmin, and phospholipolytic enzymes, such as secretory phospholipases A2 (sPLA2-IIa and sPLA2-V) and secretory acid sphingomyelinase (sSMase). Here, LDL was first proteolyzed and then subjected to lipolysis, after which the effects of combined proteolysis and lipolysis on LDL fusion and on binding to human aortic proteoglycans (PG) were studied. Chymase and cathepsin S led to more extensive proteolysis and release of peptide fragments from LDL than did plasmin. sPLA2-IIa was not able to hydrolyze unmodified LDL, and even preproteolysis of LDL particles failed to enhance lipolysis by this enzyme. However, preproteolysis with chymase and cathepsin S accelerated lipolysis by sPLA2-V and sSMase, which resulted in enhanced fusion and proteoglycan binding of the preproteolyzed LDL particles. Taken together, the results revealed that proteolysis sensitizes the LDL particles to hydrolysis by sPLA2-V and sSMase. By promoting fusion and binding of LDL to human aortic proteoglycans, the combination of proteolysis and phospholipolysis of LDL particles potentially enhances extracellular accumulation of LDL-derived lipids during atherogenesis. |
| first_indexed | 2024-12-14T04:00:37Z |
| format | Article |
| id | doaj.art-5139313bc0274484b64f94a94f560b4a |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T04:00:37Z |
| publishDate | 2010-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-5139313bc0274484b64f94a94f560b4a2022-12-21T23:17:57ZengElsevierJournal of Lipid Research0022-22752010-07-0151718011809Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinaseRiia Plihtari0Eva Hurt-Camejo1Katariina Öörni2Petri T. Kovanen3Wihuri Research Institute, Helsinki, FinlandAstraZeneca, Bioscience, Mölndal and Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, SwedenTo whom correspondence should be addressed; Wihuri Research Institute, Helsinki, FinlandWihuri Research Institute, Helsinki, FinlandLDL particles that enter the arterial intima become exposed to proteolytic and lipolytic modifications. The extracellular hydrolases potentially involved in LDL modification include proteolytic enzymes, such as chymase, cathepsin S, and plasmin, and phospholipolytic enzymes, such as secretory phospholipases A2 (sPLA2-IIa and sPLA2-V) and secretory acid sphingomyelinase (sSMase). Here, LDL was first proteolyzed and then subjected to lipolysis, after which the effects of combined proteolysis and lipolysis on LDL fusion and on binding to human aortic proteoglycans (PG) were studied. Chymase and cathepsin S led to more extensive proteolysis and release of peptide fragments from LDL than did plasmin. sPLA2-IIa was not able to hydrolyze unmodified LDL, and even preproteolysis of LDL particles failed to enhance lipolysis by this enzyme. However, preproteolysis with chymase and cathepsin S accelerated lipolysis by sPLA2-V and sSMase, which resulted in enhanced fusion and proteoglycan binding of the preproteolyzed LDL particles. Taken together, the results revealed that proteolysis sensitizes the LDL particles to hydrolysis by sPLA2-V and sSMase. By promoting fusion and binding of LDL to human aortic proteoglycans, the combination of proteolysis and phospholipolysis of LDL particles potentially enhances extracellular accumulation of LDL-derived lipids during atherogenesis.http://www.sciencedirect.com/science/article/pii/S0022227520371029proteolytic enzymesatherosclerosislow-density lipoprotein |
| spellingShingle | Riia Plihtari Eva Hurt-Camejo Katariina Öörni Petri T. Kovanen Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase Journal of Lipid Research proteolytic enzymes atherosclerosis low-density lipoprotein |
| title | Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase |
| title_full | Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase |
| title_fullStr | Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase |
| title_full_unstemmed | Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase |
| title_short | Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase |
| title_sort | proteolysis sensitizes ldl particles to phospholipolysis by secretory phospholipase a2 group v and secretory sphingomyelinase |
| topic | proteolytic enzymes atherosclerosis low-density lipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520371029 |
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