Hypoxia-ischemia in perinatal rat brain induces the formation of a low molecular weight isoform of striatal enriched tyrosine phosphatase (STEP)

Protein tyrosine phosphatases play a critical role in controlling tyrosine phosphorylation levels of proteins. Ischemia induces changes in tyrosine ph osphorylation. As part: of our investigations of the mechanisms responsible for these changes, we studied the effects of cerebral hypoxia-ischemia in 7-day-old (P7) and P21 rat brains on expression of the STEP (striatal enric hed phosphatase) family of protein tyrosine phosphatases. P7 and P21 rats w ere subjected to unilateral hypoxia-ischemia, and brains were analyzed at v arious intervals of recovery for the presence of STEP. Hypoxia-ischemia ind uced the formation of a low M-r isoform of STEP, STEP33, in the ipsilateral (damaged) hemisphere but not in the contralateral (undamaged) side. STEP33 produced as a result of ischemia was located exclusively in the cell solub le fraction, In P21 vats, the ischemia-induced elevation in STEP33 was dela yed relative to P7 rats. STEP33 was produced by digestion of postsynaptic d ensities with calpain I and by exposure of NT2/D1 cells expressing STEP to the calcium ionophore A23187. The results suggest that ischemia-induced cal cium influx results in the calcium-dependent proteolysis of membrane-associ ated STEP61 and the concomitant release of STEP33 into the cytoplasm.