Activation of PKC-epsilon counteracts maturation and apoptosis of HL-60 myeloid leukemic cells in response to TNF family members

Protein kinase C (PKC)-epsilon, a component of the serine/threonine PKC family, has been shown to influence the survival and differentiation pathways of normal hematopoietic cells. Here, we have modulated the activity of PKC-epsilon with specific small molecule activator or inhibitor peptides. PKC-e...

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Bibliographic Details
Published in:European journal of histochemistry 2009-09, Vol.53 (3), p.177
Main Authors: Gonelli, A, Milani, D, Rimondi, E, Voltan, R, Grill, V, Celeghini, C
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Cell Differentiation - drug effects
Enzyme Activation
HL-60 Cells
Humans
Protein Kinase C-epsilon - antagonists & inhibitors
Protein Kinase C-epsilon - metabolism
TNF-Related Apoptosis-Inducing Ligand - pharmacology
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Protein kinase C (PKC)-epsilon, a component of the serine/threonine PKC family, has been shown to influence the survival and differentiation pathways of normal hematopoietic cells. Here, we have modulated the activity of PKC-epsilon with specific small molecule activator or inhibitor peptides. PKC-epsilon inhibitor and activator peptides showed modest effects on HL-60 maturation when added alone, but PKC-epsilon activator peptide significantly counteracted the pro-maturative activity of tumor necrosis factor (TNF)-alpha towards the monocytic/macrophagic lineage, as evaluated in terms of CD14 surface expression and morphological analyses. Moreover, while PKC-epsilon inhibitor peptide showed a reproducible increase of TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis, PKC-epsilon activator peptide potently counteracted the pro-apoptotic activity of TRAIL. Taken together, the anti-maturative and anti-apoptotic activities of PKC-epsilon envision a potentially important proleukemic role of this PKC family member.
ISSN:1121-760X
2038-8306
DOI:10.4081/ejh.2009.177