Overexpression of Protein Kinase C Isoform  but not δ in Human Interleukin-3–Dependent Cells Suppresses Apoptosis and Induces bcl-2 Expression

Abstract

Hematopoietic progenitor cells die by apoptosis after removal of the appropriate colony-stimulating factor (CSF). Recent pharmacologic data have implicated protein kinase C (PKC) in the suppression of apoptosis in interleukin-3 (IL-3) and granulocyte-macrophage (GM)-CSF–dependent human myeloid cells. Because IL-3 and GM-CSF induce increases in diacylglycerol without mobilizing intracellular Ca++, it seemed that one of the novel Ca++ independent isoforms of PKC was involved. We report here that overexpression of PKC in factor-dependent human TF-1 cells extends cell survival in the absence of cytokine. Overexpression of PKCδ does not have this effect. By 72 to 96 hours after cytokine withdrawal, the PKC transfectants remain distributed in all phases of the cell cycle, as shown by fluorescence-activated cell sorting (FACS) analysis, while little intact cellular DNA is detectable in vector or PKCδ transfectants. PKC induces bcl-2 protein expression fivefold to sixfold over the levels in empty vector transfectants, whereas the levels in PKCδ transfectants are similar to those in vector controls.

Substance P protects spiral ganglion neurons from apoptosis via PKC‐Ca2+‐MAPK/ERK pathways

“…The effect of bisindolylmaleimide I on SP-mediated survival effect on SGNs suggest a direct role for PKC in the NK1 activation-mediated signalling pathway, as previously shown by Yang and colleagues in human tracheal smooth muscle cells (Yang et al 2002). This is in agreement with previous reports showing that cellular PKC activity can protect cells against a variety of apoptotic stimuli (Mcconkey et al 1989;Gubina et al 1998). Gö 6976 is an indolocarbazole generated from staurosporine and showing good selectivity for PKC over other protein kinases and discriminates between cPKC isoforms, Ca 2+ -dependent, and nPKC (Martiny-Baron et al 1993), targeting specifically PKCa and bI.…”

Neuroprotection via pro‐survival protein kinase C isoforms associated with Bcl‐2 family members

“…The present data complement previous observations showing that certain PKC isoforms are intimately involved in cell survival/death signals that protect against cell death. Thus, PKCα is known to phosphorylate Bcl-2 in a site that increases its anti-apoptotic function (34), and overexpression of PKCε results in increased expression of Bcl-2 (35). Furthermore, suppression of PKCα triggers apoptosis through down-regulation of Bcl-xL (36).…”

Novel Neuroprotective Mechanism of Action of Rasagiline Is Associated with Its Propargyl Moiety: Interaction of Bcl-2 Family Members with PKC Pathway

“…Thus, PKCα is known to phosphorylate Bcl-2 in a site that increases its antiapoptotic function, 23 and overexpression of PKCε results in increased expression of Bcl-2. 24 Moreover, suppression of PKCα triggers apoptosis through downregulation of Bcl-X L . 25 In addition, MAPK/ERK cascades, which have been shown to inhibit cell death in a number of systems, can be activated by PKC.…”