Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor

Science. 1996 Jul 26;273(5274):503-7. doi: 10.1126/science.273.5274.503.

Abstract

B and T lymphocytes undergoing apoptosis in response to anti-immunoglobulin M antibodies and dexamethasone, respectively, were found to have increased amounts of messenger RNA for the inositol 1,4,5-trisphosphate receptor (IP3R) and increased amounts of IP3R protein. Immunohistochemical analysis revealed that the augmented receptor population was localized to the plasma membrane. Type 3 IP3R (IP3R3) was selectively increased during apoptosis, with no enhancement of type 1 IP3R (IP3R1). Expression of IP3R3 antisense constructs in S49 T cells blocked dexamethasone-induced apoptosis, whereas IP3R3 sense, IP3R1 sense, or IP3R1 antisense control constructs did not block cell death. Thus, the increases in IP3R3 may be causally related to apoptosis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / immunology
  • Calcium Channels / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • DNA, Antisense
  • Dexamethasone / pharmacology
  • Immunoblotting
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors
  • Mice
  • Molecular Sequence Data
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / immunology
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Calcium Channels
  • DNA, Antisense
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Dexamethasone
  • Inositol 1,4,5-Trisphosphate
  • Calcium