Induction of tissue transglutaminase in response to ischemic brain injury

Tissue transglutaminase (tTG) is a member of the transglutaminase family that catalyzes the post-translational modification of proteins by inserting isopeptide bond within or between polypeptide chains in a Ca++ dependent manner. Although tTG is known to be involved in cell growth, apoptosis and neurodegeneration, the role of tTG in traumatic and ischemic brain injury (TBI and IBI) is largely unknown. Previously, we showed that tTG was up-regulated at mRNA and protein levels after TBI in rats. Although TBI and IBI can result in some common pathological sequelae, there are many important differences. Thus, we hypothesized that tTG message and protein is up-regulated after transient middle cerebral artery occlusion (MCAO), and that the magnitude and temporal expression differ from TBI. tTG protein and mRNA of ipsi-cortex and hippocampus from rats of 0, 1, 3, 5 and 7 days after MCAO were quantified by Western blot and real time PCR with tissues from similar contra-lateral areas as controls. Results showed that tTG mRNA in ipsi-cortex increased steadily from 1 to 5 days (1.5–10 fold of control level) after MCAO and dropped to control level by 7 days. In ipsi-hippocampus, tTG mRNA increased ∼2 fold of control at 1 day after MCAO and gradually returned to control level by 7 days. tTG protein levels for both ipsi-cortex and ipsi-hippocampus increased steadily during the experiment with a more significant increase in cortex (∼5.5 fold in ipsi-cortex vs. 2 fold in ipsi-hippocampus). Levels of tTG mRNA and protein of control tissues were unchanged. These results indicate that tTG after MCAO in cortex and hippocampus is up-regulated in a similar pattern to those in TBI brains. Studies of functional significance of tTG after ischemia and TBI are underway.