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Regulation of Na+-H+ exchange in normal NIH-3T3 cells and in NIH-3T3 cells expressing the ras oncogene

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:5985690
; ; ; ;
Our laboratory and others have demonstrated that Na+-H+ exchange can be regulated by two different pathways; one that is mediated by an inositol trisphosphate-stimulated increase in intracellular calcium activity, and one that is mediated by an increase in protein kinase C activity. To determine whether one of these pathways is more important than the other, or whether one pathway is physiologically relevant, we employed normal NIH-3T3 cells (3T3 cells) and NIH-3T3 cells expressing the EJ human bladder ras oncogene (EJ cells). The EJ cells were chosen because they provide a genetic model that does not exhibit serum- or platelet-derived growth factor (PDGF)-stimulated inositol trisphosphate release or Ca2+ mobilization. It was found that serum- or PDGF-stimulated Na+-H+ exchange was more pronounced in EJ cells than in control 3T3 cells. As expected, serum- or PDGF-stimulated Na+-H+ exchange in 3T3 cells was inhibited by chelating intracellular Ca2+ with the intracellular Ca2+ chelator quin2, by the intracellular Ca2+ antagonist 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), and by the calmodulin antagonist trifluoperazine. In contrast, these agents did not inhibit serum- or PDGF-stimulated Na+-H+ exchange in EJ cells. Activators of protein kinase C (e.g., 1-oleoyl-2-acetylglycerol or biologically active phorbol esters) were found to stimulate Na+-H+ exchange in EJ cells to the same extent as serum. However, these agents were considerably less effective than serum in control 3T3 cells. Despite these findings, PDGF did not stimulate diacylglycerol levels in EJ cells.
Research Organization:
Univ. of Health Sciences, Chicago Medical School, IL (USA)
OSTI ID:
5985690
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 256; ISSN AJPHA
Country of Publication:
United States
Language:
English

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560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
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ENZYME ACTIVITY
ENZYMES
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FIBROBLASTS
GENE REGULATION
GENES
HEMATOLOGIC AGENTS
HYDROGEN IONS
ION EXCHANGE
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KINETICS
LIPIDS
MAMMALS
MATERIALS
MEMBRANE TRANSPORT
MICE
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHORBOL ESTERS
PHOSPHOLIPIDS
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PHOSPHOTRANSFERASES
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RODENTS
SODIUM COMPOUNDS
SOMATIC CELLS
TRANSFERASES
URINARY TRACT
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