PMID- 2096218
OWN - NLM
STAT- MEDLINE
DCOM- 19910717
LR  - 20191029
IS  - 0887-2082 (Print)
IS  - 0887-2082 (Linking)
VI  - 5
IP  - 4
DP  - 1990 Winter
TI  - Oxidatively stressed lymphocytes remain in G0/G1a on mitogenic stimulation.
PG  - 229-35
AB  - Thiol modifiers and oxidants inhibit lymphocyte activation. To investigate which 
      of the many cell functions sensitive to oxidation are critical in this 
      inhibition, mouse splenic lymphocytes were treated with oxidants prior to 
      exposure to mitogen, and progression into the cell cycle was assayed. Different 
      treatments were used to chemically dissect different potential targets within the 
      cell: copper phenanthroline (CuP), to oxidize surface sulfhydryls; N-ethyl 
      maleimide (NEM), to alkylate extra- and intracellular thiols; and hydrogen 
      peroxide, which generates the highly reactive hydroxyl radical within the cell. 
      Progression into the cell cycle was assayed with acridine orange (AO) and assays 
      of interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression. The 
      contribution of ADP-ribosylation to inhibition of mitogenesis was assessed using 
      3-aminobenzamide (3AB) to inhibit adenosine 5'-diphosphate (ADP)-ribose 
      transferases. The results indicate that the CuP and NEM treatments both produce 
      two independent inhibitory effects, that is, a failure in the production of and 
      response to IL-2. Cells treated with these compounds were able to progress only 
      through G1a upon mitogenic stimulation. H2O2 had more complex effects. Both 
      ADP-ribosylation and modulations of cytosolic Ca2+ were involved in the 
      inhibitory effects. With lower inhibitory doses of H2O2, lymphocytes were 
      completely unresponsive to mitogen and failed to exit Go upon mitogenic 
      stimulation. If intra- and extracellular Ca2+ were buffered before treatment with 
      H2O2, higher concentrations were required, and under these conditions cells were 
      able to enter G1a but could not progress into G1b. Under neither of these 
      conditions could cells produce IL-2 or express IL-2R.
FAU - Duncan, D D
AU  - Duncan DD
AD  - Department of Microbiology and Immunology, Albany Medical College, New York 
      12208.
FAU - Lawrence, D A
AU  - Lawrence DA
LA  - eng
GR  - ES-03778/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biochem Toxicol
JT  - Journal of biochemical toxicology
JID - 8700114
RN  - 0 (Interleukin-2)
RN  - 0 (Mitogens)
RN  - 0 (Phenanthrolines)
RN  - 0 (Receptors, Interleukin-2)
RN  - 20762-30-5 (Adenosine Diphosphate Ribose)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - O3C74ACM9V (Ethylmaleimide)
RN  - W4X6ZO7939 (1,10-phenanthroline)
SB  - IM
MH  - Adenosine Diphosphate Ribose/metabolism
MH  - Animals
MH  - Ethylmaleimide/*toxicity
MH  - Female
MH  - G1 Phase/drug effects
MH  - Hydrogen Peroxide/*toxicity
MH  - Interleukin-2/biosynthesis
MH  - Lymphocyte Activation/drug effects
MH  - Lymphocytes/cytology/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Mitogens/pharmacology
MH  - Oxidation-Reduction
MH  - Phenanthrolines/*toxicity
MH  - Receptors, Interleukin-2/biosynthesis
MH  - Resting Phase, Cell Cycle/drug effects
EDAT- 1990/01/01 00:00
MHDA- 1990/01/01 00:01
CRDT- 1990/01/01 00:00
PHST- 1990/01/01 00:00 [pubmed]
PHST- 1990/01/01 00:01 [medline]
PHST- 1990/01/01 00:00 [entrez]
AID - 10.1002/jbt.2570050405 [doi]
PST - ppublish
SO  - J Biochem Toxicol. 1990 Winter;5(4):229-35. doi: 10.1002/jbt.2570050405.