Differential lymphocyte growth-modifying effects of oxidants: Changes in cytosolic Ca sup +2

Journal Article · Fri Sep 15 04:00:00 EDT 1989 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(89)90296-2· OSTI ID:5476993

Duncan, D D; Lawrence, D A ^[1]

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1. Albany Medical College, NY (USA)

An increase in the concentration of cytosolic Ca+2 ((Ca-2)i) is among the earliest changes seen in mitogen-stimulated lymphocytes and is a consequence of signal transduction which usually results in the initiation of cell cycle progression. However, increased (Ca+2)i has also been correlated with cytotoxicity. We have determined whether modulations of (Ca+2)i are involved in the functional inactivation of cells observed with sublethal concentrations of oxidants. Specifically, (Ca+2)i was measured in mouse splenic lymphocytes that were treated with different oxidants in order to determine if oxidative stress interferes with mitogen-stimulated increases in (Ca+2)i, if oxidants themselves modulated (Ca+2)i, and, if so, whether such Ca+2 modulations by oxidants had stimulatory or inhibitory effects on the response of lymphocytes to mitogens. The oxidants employed were copper phenanthroline (CuP; surface thiol oxidizer), N-ethyl maleimide (NEM; permeant thiol alkylator), hydrogen peroxide (H2O2; generates hydroxyl radical within the cell), and radiation (Cs-137; generates hydroxyl radical by radiolysis). Growth of all treated cells was equally inhibited upon stimulation with Con A or PMA/A23187, suggesting that all the oxidants inhibited cell functions required distal in activation to the transduction pathway utilized by Con A but bypassed by PMA/A23187. Doses of CuP, NEM, and radiation which fully inhibited Con A-stimulated proliferation had little effect on resting or mitogen-stimulated changes of (Ca+2)i, but H2O2 doses which fully inhibited proliferation increased (Ca+2)i in unstimulated cells and prevented the increase normally caused by Con A. Both intra- and extracellular Ca+2 contributed to the increased (Ca+2)i seen in unstimulated cells.

• OSTI ID: 5476993
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 100:3; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTIMITOTIC DRUGS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CALCIUM COMPOUNDS
CARCINOGENS
CELL PROLIFERATION
CESIUM 137
CESIUM ISOTOPES
CONCANAVALIN
CONNECTIVE TISSUE CELLS
DRUGS
ESTERS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
HYDROXYL RADICALS
IMIDES
INHIBITION
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MITOGENS
NEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDIZERS
OXYGEN COMPOUNDS
PEROXIDES
PHORBOL ESTERS
RADICALS
RADIOISOTOPES
RADIOSENSITIZERS
RODENTS
SOMATIC CELLS
SPLEEN
SYNTHESIS
VERTEBRATES
YEARS LIVING RADIOISOTOPES