We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Critical role for classical PKC in activating Akt by phospholipase A<sub>2</sub>-modified LDL in monocytic cells
- Authors
Preiß, Stefan; Namgaladze, Dmitry; Brüne, Bernhard
- Abstract
Abstract: 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 PKCα (PKCα-EGFP K368R) and PKCβ (PKCβ-EGFP K371M) constructs or with siRNA specific for PKCα/PKCβ using nucleofection technology. Cell survival was assessed by Annexin V/propidium iodide staining or mitochondrial membrane potential measurement with 3,3′-dihexyloxacarbocyanine iodide (DiOC6) 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 PKCα and overexpression of dominant-negative PKCα as well as PKCβ 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 PKCα and PKCβ are critical for PLA-LDL-induced Akt phosphorylation and survival in THP-1 monocytic cells.
- Subjects
LOW density lipoproteins; PROTEIN kinase C; PHOSPHOLIPASE A2; PROTEIN kinases
- Publication
Cardiovascular Research, 2007, Vol 73, Issue 4, p833
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2006.12.019