PubMed Health⌕ Search

PubMed · 1747427

[Change in energy metabolism of ascites cancer cells with a decrease in pH].

Abstract

In Hank's balanced salt solution EL-4 ascites thymoma cells possessed endogenous respiration which was sufficient for the maintenance of their ATP level: pH decrease down to 6.0 had no effect either on endogenous respiration or the ATP level. Glucose had no influence on the respiration of EL-4 cells but inhibited that of Ehrlich ascites carcinoma (EAC) cells by 40% (Crabtree effect); respiration of the both cell lines was strongly (4-fold) inhibited after simultaneous addition of glucose, lactate and pH decrease. EL-4 cells had no endogenous glycolysis; EAC cells showed a low level of glycolysis only after pH decrease. Glucose addition led to activation of glycolysis (both inhibited 2-fold after a decrease of pH down to 6.0. The respiration inhibition at pH 7.3 and 6.0 caused no decrease of ATP depletion when glucose was present in the medium; this result may be due to suppression of ATP consumption. Incubation of EL-4 cells under respiration and glycolysis deficiency conditions resulted in a sharp ATP depletion; pH decrease delayed this depletion.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

V L Gabaĭ, A F Mosin. 1991. [Change in energy metabolism of ascites cancer cells with a decrease in pH].. https://pubmed.ncbi.nlm.nih.gov/1747427/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

The human mitochondrial genome contains a second light strand promoter.

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.

Adenosine Triphosphate↗

GCN2 kinase activation by ATP-competitive kinase inhibitors.

Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib. Loss of general control nonderepressible 2 (GCN2) kinase rendered cells resistant to neratinib, whereas depletion of the GADD34 phosphatase increased neratinib sensitivity. Loss of GCN2 conferred neratinib resistance by preventing binding and activation of GCN2 by neratinib. Several other Food and Drug Administration (FDA)-approved inhibitors, such erlotinib and sunitinib, also bound and activated GCN2. Our results highlight the utility of genome-wide functional screens to uncover novel mechanisms of drug action and document the role of the integrated stress response (ISR) in modulating the response to inhibitors of oncogenic kinases.

Adenosine Triphosphate↗

Nitration of N-methyl-D-aspartate receptor subunits following in vitro dephosphorylation of cerebral cortical membranes of newborn piglets.

Previous studies have shown that activity of the cerebral N-methyl-D-aspartate (NMDA) receptor is modified by receptor nitration and phosphorylation. Since the sites for tyrosine phosphorylation and nitration are on adjacent carbon atoms, the present study tested the hypothesis that in vitro dephosphorylation of the NR1, NR2A and NR2B subunits of the NMDA receptor increases receptor nitration by peroxynitrite in cortical membranes of newborn piglets. To test this hypothesis, cerebral cortical P(2) membranes were prepared from normoxic and hypoxic newborn piglets and divided into dephosphorylated and non-dephosphorylated control groups. Dephosphorylation was performed in vitro by incubation with protein tyrosine phosphatase 1B and confirmed by immunoprecipitation with antiphosphotyrosine antibody. Dephosphorylated and non-dephosphorylated samples were nitrated with 0.5 mM peroxynitrite. Nitration was measured by immunoprecipitating with agarose-conjugated anti-nitrotyrosine antibody followed by Western blot analysis using specific anti -NR1, -NR2A and -NR2B primary antibodies. The data demonstrate that nitration of the NR1, NR2A and NR2B subunits of the NMDA receptor increases following dephosphorylation in both normoxic and hypoxic animals, however increase is much higher in hypoxic animals. We conclude that dephosphorylation at the site adjacent to the nitration site (ortho-position) on tyrosine residues of the NMDA receptor enhances nitration. Since in vitro nitration of the NMDA receptor increases the affinity of the glutamate recognition site and the receptor ion channel, we speculate that tyrosine dephosphorylation of the NMDA receptor will remove steric hindrance and facilitate nitration of tyrosine residues resulting in increased ion-channel activation in the hypoxic newborn brain.

Adenosine Triphosphate↗