Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 3 (IL-3) stimulates the growth of various types of hemopoietic progenitors. In vitro, survival of a series of murine cell lines derived from either neoplastic or nonneoplastic hemopoietic tissue shows a strict IL-3 dependence. In order to test the implication of energy metabolism in this dependence as claimed in several studies, intracellular ATP levels as well as accumulative lactate release were measured in the murine hemopoietic lines FDC-P1, 32Dcl.23, DA-1, DA-3, NFS-60, and NFS-78. ATP levels showed little or no changes within 4-6 h of IL-3 starvation. In the absence of IL-3 the accumulative lactate release ranged from 1.4 to 2.6 mM, and in its presence values between 1.5 and 3.4 mM were recorded within 7 h. Only 32Dcl.23 showed an almost complete suppression of lactate release upon IL-3 withdrawal. The cell cycle times of these cell lines determined by flow cytometry ranged between 9 (DA-3) and 24 h (NFS-78). In the presence of IL-3 there was a significant inverse relationship between cell cycle times and lactate production. It is concluded that neither ATP generation nor the metabolic pathway of lactate production, although the latter correlated with proliferative activity in the studied cell lines, is controlled by IL-3. Furthermore, no control by IL-3 of essential amino acid incorporation into proteins was detected in cell lines 32Dcl.23 and NFS-60.
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PMID:Lactate production and amino acid incorporation in interleukin 3-dependent, factor-deprived hemopoietic murine cell lines. 220 20

We have investigated phosphatidylinositol 3-kinase (PI3K)-dependent survival signalling pathways using several cytokines in three different hemopoietic cell lines, MC/9, FDC-P1, and TF-1. Cytokines caused PI3K- and PKB-dependent phosphorylation of FOXO3a (previously known as FKHRL1) at three distinct sites. Following cytokine withdrawal or PI3K inhibition, both of which are known to lead to apoptosis, there was a loss of FOXO3a phosphorylation, and a resulting increase in forkhead transcriptional activity, along with increased expression of Fas Ligand (FasL), which could be detected at the cell surface. Concurrently, an increase in cell surface expression of Fas was also detected. Despite the presence of both FasL and Fas, there was no detectable evidence that activation of Fas-mediated apoptotic events was contributing to apoptosis resulting from cytokine starvation or inhibition of PI3K activity. Thus, inhibition of FOXO3a activity is mediated by the PI3K-PKB pathway, but regulation of FasL is not the primary means by which cell survival is regulated in cytokine-dependent hemopoietic cells. We were also able to confirm increased expression of known FOXO3a targets, Bim and p27kip1. Together, these results support the conclusion that mitochondrial-mediated signals play the major role in apoptosis of hemopoietic cells due to loss of cytokine signalling.
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PMID:Cytokine-mediated FOXO3a phosphorylation suppresses FasL expression in hemopoietic cell lines: investigations of the role of Fas in apoptosis due to cytokine starvation. 1760 40