Protein kinase C activation promotes cell survival in mature lymphocytes prone to apoptosis

Lucas, Miguel; Sánchez-Margalet, Vı́ctor; Sanz, Aureo; Solano, Francisco

doi:10.1016/0006-2952(94)90129-5

Cited by 45 publications

(19 citation statements)

References 21 publications

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“…Addition of PMA after UV irradiation also seemed to reduce the number of cells showing overt apoptotic morphology, which is consistent with the known antiapoptotic effects of PKC. 9 HeLa cells labelled with an irrelevant antibody of the same isotype and same concentration as that used in Figures 3 and 4 showed no peroxidase staining (photographs not shown). Figure 4e shows that the externalization of PKC-a seen by immunocytochemistry in HeLa cells was confirmed by the immunoblot method.…”

Section: Resultsmentioning

confidence: 90%

Externalization of host cell protein kinase C during enteropathogenic Escherichia coli infection

Crane

Vezina

2004

Cell Death Differ

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Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children in developing countries. Protein kinase C (PKC), a serine-and threonine-directed protein kinase, is rapidly activated following EPEC infection and this is accompanied by its translocation to a membrane-bound location where it is tightly bound to phosphatidylserine (PS). EPEC infection causes host cell death, one of whose features is externalization of PS. We hypothesized that externalization of PS would be accompanied by externalization of PKC as well. We report that EPEC infection triggers the externalization of PKC to the outer surface of the host cell. Ecto-PKC remains firmly tethered to the cell but can be released by incubation with peptide or protein substrates for the enzyme. Ecto-PKC is intact and biologically active and able to phosphorylate protein substrates on the surface of the host cell. Phosphorylation of whole EPEC bacteria or EPEC-secreted proteins could not be detected. Externalization of PKC could be reproduced by the combination of an apoptotic stimulus (ultraviolet (UV) irradiation) and phorbol myristate acetate (PMA), a procedure which resulted in externalization of 425% of the total cellular content of PKC-a. In the presence of ATP, ecto-PKC inhibited UVinduced cell shrinkage, membrane blebbing, and propidium iodide uptake but not the activation of caspases 3 and 7. This is the first report that expression of an ecto-protein kinase is altered by a microbial pathogen and the first to note that externalization of PKC can accompany apoptosis.

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Section: Resultsmentioning

confidence: 90%

Externalization of host cell protein kinase C during enteropathogenic Escherichia coli infection

Crane

Vezina

2004

Cell Death Differ

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“…The apoptotic program can be modulated, since apoptosis is the result of a complex series of events which can be activated by many diverging stimuli. Thus, the apoptotic process can be suppressed by inhibiting protein synthesis [1,2] or via enforced expression of bcl-2 [3,4], and accelerated [5,6] or reduced [7,8] by changing the level of protein phosphorylation. These are only a few examples, among many others, which point out that once the initial damage has been inflicted, the cell undergoes a series of events that can either be blocked at different levels or ultimately lead to apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Prevention of necrosis and activation of apoptosis in oxidatively injured human myeloid leukemia U937 cells

et al. 1996

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A 3 h exposure to 1 mM H202 followed by 6 h postchallenge growth in peroxide-free medium induces necrosis in U937 cells. Addition of the poly(ADP-ribose)polymerase inhibitor 3-aminobenzamide during recovery prevents necrosis and triggers apoptosis, as shown by the appearance of apoptotie bodies, extensive blebbing and formation of multimeric DNA fragments as well as 50 kb double stranded DNA fragments. Thus, the same initial damage can be a triggering event for both apoptotic and necrotic cell death. Furthermore, necrosis does not appear to be a passive response to overwhelming damage.

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“…Cross-linking of antigen receptors in B lymphocytes causes activation of PKC with subsequent activation of many genes [17]. Previous investigators have demonstrated that mature lymphocytes are generally resistant to glucocorticoid-induced apoptosis; however, when these cells are further exposed to PKC inhibitors, apoptosis occurs [18]. Studies investigating neoplastic lymphocytes also showed that the protective, anti-apoptotic effect of PKC was present in malignant lymphoproliferative disorders and strengthened the argument of utilizing PKC inhibitors as potential therapeutic agents [6,7].…”

Section: Discussionmentioning

confidence: 99%

“…PKC activation by phorbol esters (PMA) increases the survival of CLL cells [6,18]. Consequently, we were interested in the effects of PKC inhibition in CLL cells.…”

Section: Safingol Treatment Induces Apoptosis In Cll Cellsmentioning

confidence: 99%

Survival role of protein kinase C (PKC) in chronic lymphocytic leukemia and determination of isoform expression pattern and genes altered by PKC inhibition

et al. 2005

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Recent studies have suggested that protein kinase C (PKC) activation plays an important role in survival of chronic lymphocytic leukemia (CLL). In order to characterize the role of PKC in CLL, we investigated the expression pattern of PKC isoforms in CLL cells (7 cases) and evaluated the effect of PKC inhibition on the survival of CLL cells (20 cases). Expression of the classical PKC isoforms b and g, the novel isoform d and the atypical isoform z was seen in all analyzed patient samples by Western blot analysis. Expression of the PKC isoforms a, e, and i was variable. Following incubation with the PKC inhibitor, safingol, CLL cells underwent marked apoptosis in all cases. In order to characterize the molecular events associated with the apoptotic effect of PKC inhibition, gene expression patterns in CLL cells were evaluated by cDNA-microarray analysis. Following safingol treatment, several genes showed marked downregulation and PKCrelated proteins demonstrated decreased hybridization signals. Among these proteins, CREB and Daxx were further studied by using Western blotting, nuclear binding assay and confocal immunofluorescent microscopy. These studies showed significant inhibition of these proteins, consistent with the results of microarray gene analysis. Overall, these findings suggest that PKC activation is important for CLL cell survival and that inhibitors of PKC may have a role in the treatment of patients with CLL. Am.

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Protein kinase C activation promotes cell survival in mature lymphocytes prone to apoptosis

Cited by 45 publications

References 21 publications

Externalization of host cell protein kinase C during enteropathogenic Escherichia coli infection

Externalization of host cell protein kinase C during enteropathogenic Escherichia coli infection

Prevention of necrosis and activation of apoptosis in oxidatively injured human myeloid leukemia U937 cells

Survival role of protein kinase C (PKC) in chronic lymphocytic leukemia and determination of isoform expression pattern and genes altered by PKC inhibition

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