Activation of cyclic nucleotide phosphodiesterase from isolated human peripheral blood lymphocytes by mitogenic agents

P. M. Epstein, J. S. Mills, Evan M Hersh, S. J. Strada, W. J. Thompson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

During long-term incubation of human peripheral blood lymphocytes with phytohemagglutinin (PHA), adenosine cyclic 3':5'-monophosphate (cyclic AMP) phosphodiesterase increases about 5-fold and guanosine cyclic 3':5'-monophosphate (cyclic GMP) phosphodiesterase increases about 10-fold in specific activity. Under similar conditions, there is little change in either basal or fluoride-stimulated adenylyl cyclase activity. The increase in cyclic nucleotide phosphodiesterase activity also occurs with other mitogenic activators of blastogenesis including concanavalin A, pokeweed mitogen, and Streptolysin O. Cyclic AMP phosphodiesterase activity in PHA-stimulated lymphocytes displays an increase in maximum velocity but no change in other kinetic properties when compared to that of unstimulated lymphocytes. Linear density gradient analyses of cyclic nucleotide phosphodiesterases in mitogen-stimulated lymphocytes show an increased activity in lower (3.6S) and higher (5.9S) molecular weight forms of cyclic AMP and cyclic GMP phosphodiesterase. Hydroxyurea inhibits PHA-induced mitogenesis but has no effect on the observed increase in phosphodiesterase activity. 1-Methyl-3-isobutylxanthine inhibits PHA-induced mitogenesis and prevents the increase in cyclic GMP phosphodiesterase activity, but the increase in cyclic AMP phosphodiesterase activity is greater than that seen with PHA alone. The PHA-induced increase in cyclic AMP and cyclic GMP phosphodiesterase activity is inhibited by cycloheximide; however, Actinomycin D does not completely inhibit PHA stimulation of cyclic nucleotide phosphodiesterase activity when it is used at a concentration that inhibits the PHA-induced increase in [ 3H]-thymidine and [ 3H]uridine incorporation by greater that 90%. These results indicate that de novo protein synthesis but not mitogenesis per se is required for the increased enzyme activity induced by mitogenic agents. The results are discussed with respect to the regulation of cyclic nucleotide phosphodiesterase and to the role of these enzymes in lymphocyte proliferation.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalCancer Research
Volume40
Issue number2
StatePublished - 1980
Externally publishedYes

Fingerprint

Cyclic Nucleotides
Phosphoric Diester Hydrolases
Phytohemagglutinins
Lymphocytes
Cyclic AMP
Cyclic GMP
1-Methyl-3-isobutylxanthine
Pokeweed Mitogens
Hydroxyurea
Guanosine
Uridine
Dactinomycin
Enzymes
Cycloheximide
Lymphocyte Activation
Concanavalin A
Fluorides
Mitogens
Adenylyl Cyclases
Adenosine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Activation of cyclic nucleotide phosphodiesterase from isolated human peripheral blood lymphocytes by mitogenic agents. / Epstein, P. M.; Mills, J. S.; Hersh, Evan M; Strada, S. J.; Thompson, W. J.

In: Cancer Research, Vol. 40, No. 2, 1980, p. 379-386.

Research output: Contribution to journalArticle

Epstein, P. M. ; Mills, J. S. ; Hersh, Evan M ; Strada, S. J. ; Thompson, W. J. / Activation of cyclic nucleotide phosphodiesterase from isolated human peripheral blood lymphocytes by mitogenic agents. In: Cancer Research. 1980 ; Vol. 40, No. 2. pp. 379-386.
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