| Critical role for classical PKC in activating Akt by phospholipase A2-modified LDL in monocytic cells. | |
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MedLine Citation:
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PMID: 17261275 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Modification of low density lipoprotein (LDL) by phospholipases confers pro-atherogenic properties, although signalling pathways of phospholipase-modified LDL (PLA-LDL) remain obscure. We questioned whether members of the protein kinase C (PKC) family are involved in PLA-LDL-induced Akt phosphorylation and survival of THP-1 monocytic cells. METHODS: Akt phosphorylation in THP-1 cells was monitored by Western analysis. To modulate PKC expression cells were transfected with dominant-negative enhanced green fluorescent protein linked PKCalpha (PKCalpha-EGFP K368R) and PKCbeta (PKCbeta-EGFP K371M) constructs or with siRNA specific for PKCalpha/PKCbeta using nucleofection technology. Cell survival was assessed by Annexin V/propidium iodide staining or mitochondrial membrane potential measurement with 3,3'-dihexyloxacarbocyanine iodide (DiOC(6)) using flow cytometry. RESULTS: Inhibitors of phospholipase C (PLC) or classical PKCs as well as PKC depletion following phorbol ester treatments, blocked Akt phosphorylation in response to PLA-LDL. In contrast, phosphatidylinositol 3-kinase (PI3K) activation by PLA-LDL was insensitive to PKC inhibition. Using RNA interference to knockdown PKCalpha and overexpression of dominant-negative PKCalpha as well as PKCbeta drastically lowered Akt phosphorylation after PLA-LDL. Moreover, inhibition of PKC attenuated a PLA-LDL-induced survival response towards oxidative stress in THP-1 cells. CONCLUSION: We show that PKCalpha and PKCbeta are critical for PLA-LDL-induced Akt phosphorylation and survival in THP-1 monocytic cells. |
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Authors:
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Stefan Preiss; Dmitry Namgaladze; Bernhard Brüne |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-30 |
Journal Detail:
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Title: Cardiovascular research Volume: 73 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-02-19 Completed Date: 2007-05-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 833-40 Citation Subset: IM |
Affiliation:
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Faculty of Medicine, Institute of Biochemistry I, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western
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methods Cell Line, Tumor Green Fluorescent Proteins / genetics Group IV Phospholipases A2 Humans Lipoproteins, LDL / metabolism* Microscopy, Fluorescence Monocytes / metabolism* Phospholipases A / metabolism* Phospholipases A2 Protein Kinase C / genetics, physiology* Proto-Oncogene Proteins c-akt / metabolism* RNA, Small Interfering / pharmacology Signal Transduction / physiology* Transfection / methods |
| Chemical | |
Reg. No./Substance:
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0/Lipoproteins, LDL; 0/RNA, Small Interfering; 0/low density lipoprotein inhibitor; 147336-22-9/Green Fluorescent Proteins; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.13/Protein Kinase C; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Group IV Phospholipases A2; EC 3.1.1.4/Phospholipases A2 |
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