PMID: 9657740Jul 10, 1998Paper

Granulocyte-macrophage colony-stimulating factor rescues TF-1 leukemia cells from ionizing radiation-induced apoptosis through a pathway mediated by protein kinase Calpha.

Blood
M L KellyBarbara S Beckman

Abstract

Protein kinase C (PKC) activity has a recognized role in mediating apoptosis. However, the role of individual PKC isoforms in apoptosis is poorly defined. Therefore, we investigated the translocation of individual PKC isoforms during radiation-induced apoptosis with and without rescue from apoptosis by granulocyte-macrophage colony-stimulating factor (GM-CSF) in the human erythroleukemia cell line TF-1. PKCalpha was translocated from the particulate to cytosolic fraction of TF-1 cells within 5 minutes of treatment with apoptosis-inducing levels of ionizing radiation. However, this postirradiation translocation did not occur when cells were rescued from apoptosis by GM-CSF. Furthermore, treatment of cells with Gö 6976, an inhibitor of classical PKC isoforms, abrogated the rescue effect of GM-CSF. The calcium-independent novel PKC isoform, PKCalpha appeared to be degraded in both the particulate and cytosolic fractions of TF-1 cells after treatment with apoptosis-inducing levels of ionizing radiation in either the presence or absence of GM-CSF rescue. Levels of ceramide, a lipid mediator of apoptosis, were measured at 2, 4, 8, 10, and 60 minutes after treatment with ionizing radiation and were substantially reduced in TF-1 cells ...Continue Reading

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