Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor.
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.
Khan
A A
AA
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Soloski
M J
MJ
Sharp
A H
AH
Schilling
G
G
Sabatini
D M
DM
Li
S H
SH
Ross
C A
CA
Snyder
S H
SH
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D016373:DNA, Antisense; D003907:Dexamethasone / Q000494:pharmacology; D015151:Immunoblotting; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D016373:DNA, Antisense; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D003907:Dexamethasone; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium