Induction of inositol 1,4,5 trisphosphate receptor genes by ionizing radiation.
We used differential display, a method designed to amplify partial cDNA sequences from subsets of mRNAs, to identify mRNAs induced by ionizing radiation in human Epstein Barr Virus (EBV)-transformed lymphoblastoid cells. Increased expression of a cDNA corresponding to the inositol 1,4,5 trisphosphate receptor (InsP3R) type 1 was observed after exposure of cells to 3Gy gamma-rays. This was confirmed by Northern blot analysis. The increase in mRNA for InsP3R type 1 was accompanied by a corresponding increase in the level of InsP3R type 1 protein as determined by Western blotting. Exposure of cells from patients with the human genetic disorder ataxia-telangiectasia (A-T), characterized by hypersensitivity to ionizing radiation, failed to change the levels of InsP3R type 1 mRNA and, as expected, there was no increase in InsP3R type 1 protein in A-T cells in response to radiation exposure. Protein levels for two other InsP3Rs, types 2 and 3, were observed to increase in control and A-T cells after exposure to ionizing radiation. The induction of the InsP3R type 1, which is primarily located in the endoplasmic reticulum, may play an important role in radiation signal transduction.
Yan
J
J
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Royal Brisbane Hospital, Australia.
Khanna
K K
KK
Lavin
M F
MF
D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011839:Radiation, Ionizing; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015398:Signal Transduction
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D002118:Calcium