v-Abl protein tyrosine kinase (PTK) mediated suppression of apoptosis is associated with the up-regulation of Bcl-XL

Abstract

We demonstrated previously that the activation of v-Abl protein tyrosine kinase (PTK) in IC.DP murine pre-mast cells resulted in suppression of apoptosis after withdrawal of interleukin 3 (IL-3), that protein kinase C (PKC) translocated to the nucleus 6 h after v-Abl PTK activation and that inhibition of PKC restored apoptosis after IL-3 deprivation in the presence of v-Abl PTK activity. Here we demonstrate that v-Abl PTK activation is followed by an approximately twofold increase in mRNA level of Bcl-X L by 6 h and a corresponding increase in Bcl-X L protein level by 24 h. Bcl-x L RNA and protein decreased in IL-3 deprived cells in the absence of v-Abl PTK activity. Exposure of cells with v-Abl PTK active to the PKC inhbitor calphostin C (125 ng/ml) prevented the increase in Bcl-x L protein and resulted in apoptosis. No changes in Bax or Bcl-2 protein level were noted after IL-3 withdrawal and/or activation of v-Abl PTK. Bak was barely detectable and Bad protein level decreased in cells undergoing apoptosis. The data suggest that suppression of apoptosis by v-Abl PTK in the absence of IL-3 is associated with PKC signalling and the upregulation of Bcl-x L in IC.DP cells.

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

“…This is in agreement with our results showing the dramatic reduction of Bcl-x expression in Ba/F3D749 cells in absence of IL-3. Similarly, it has been shown that suppression of apoptosis mediated by Bcr-abl or v-abl was independent of Bcl-2 expression but was correlated with up-regulation of Bcl-x L (Amarente- Mendes et al, 1998;Chen et al, 1997). Altogether these results support our data that inhibition of Bcl-x by the dominant negative form of STAT5 coincide with an increase of apoptosis in Ba/F3 cells in absence of IL-3.…”

Enhancement of Mast Cell Survival: A Novel Function of Some Secretory Phospholipase A2 Isotypes

“…Activation of tyrosine kinases and phosphoinositide 3Ј-kinase (PI3Ј-K) has been implicated in the induction of mast cell growth (19 -21). Other studies have shown a decrease in the protooncogene bcl-2 after removal of IL-3; moreover, overexpression of bcl-2 prolongs the survival of mast cells after IL-3 removal (22)(23)(24)(25)(26)(27)(28)(29). In contrast, SCF does not appear to influence bcl-2 expression (14).…”

Redox status of thioredoxin-1 (TRX1) determines the sensitivity of human liver carcinoma cells (HepG2) to arsenic trioxide-induced cell death

“…As 2 O 3 -treated cells were fractionated by differential centrifugation as described previously [43][44][45]. Briefly, cells were harvested through trypsin digestion, and then centrifuged and resuspended in three volumes of hypotonic buffer (210 mM sucrose, 70 mM mannitol, 10 mM HEPES (pH 7.4), 1 mM EDTA) containing 1 mM PMSF, 50 mg/ml trypsin inhibitor, 10 mg/ml leupeptin, 5 mg/ml aprotinin and 10 mg/ml pepstatin.…”