PDE7A is expressed in human B-lymphocytes and is up-regulated by elevation of intracellular cAMP

Cell Signal. 2002 Mar;14(3):277-84. doi: 10.1016/s0898-6568(01)00250-9.

Abstract

PDE7A is a recently described 3',5'-cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) whose expression has been detected in T-cells. As treatment with the methylxanthine theophylline, a nonspecific PDE inhibitor, induces apoptosis in leukemic cells from patients with the B-lineage malignancy chronic lymphocytic leukemia (CLL), we sought to determine if PDE7A was a target of theophylline therapy in such cells. Western analysis revealed expression of PDE7A in normal human splenic B-cells, primary CLL cells, and in a CLL-derived cell line (WSU-CLL). Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines. The activity of PDE7A isolated from the WSU-CLL cell line by immunoprecipitation was inhibited by theophylline and IBMX with IC50 values of 343.5 and 8.6 microM, respectively. WSU-CLL PDE7A was also up-regulated by a novel specific inhibitor (IC242), which inhibits PDE7A from WSU-CLL cells with an IC50 value of 0.84 microM. IC242-mediated up-regulation of PDE7A was blocked by the protein kinase A (PKA) inhibitor H-89.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / genetics
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / enzymology*
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Dose-Response Relationship, Drug
  • Humans
  • Intracellular Fluid
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Phosphodiesterase Inhibitors / pharmacology
  • Purinergic P1 Receptor Antagonists
  • Spleen / cytology
  • Theophylline / pharmacology
  • Tumor Cells, Cultured
  • Up-Regulation*
  • Xanthines / pharmacology

Substances

  • Phosphodiesterase Inhibitors
  • Purinergic P1 Receptor Antagonists
  • Xanthines
  • Colforsin
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Theophylline
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE3B protein, human
  • PDE4A protein, human
  • PDE4B protein, human
  • PDE4D protein, human
  • 1-Methyl-3-isobutylxanthine