Selective Gene Expression in Focal Cerebral Ischemia

Abstract

Regional patterns of protein synthesis were examined in rat cortex made ischemic by the occlusion of the right common carotid and middle cerebral arteries. At 2 h of ischemia, proteins were pulse labeled with intracortical injections of a mixture of [³H]leucine, [³H]isoleucine, and [³H]proline. Newly synthesized proteins were analyzed by two-dimensional gel fluorography, and the results correlated with local CBF, measured with [¹⁴C]iodoantipyrine as tracer. Small blood flow reductions (CBF = 50–80 ml 100 g⁻¹ min⁻¹) were accompanied by a modest inhibition in synthesis of many proteins and a marked increase in one protein (M_r 27,000). With further reduction in blood flow (CBF = 40 ml 100 g⁻¹ min⁻¹), synthesis became limited to a small group of proteins (M_r 27,000, 34,000, 73,000, 79,000, and actin) including two new polypeptides (M_r 55,000 and 70,000). Severe ischemia (CBF = 15–25 ml 100 g⁻¹ min⁻¹) caused the isoelectric modification of several proteins (M_r 44,000, 55,000, and 70,000) and induced synthesis of another protein (M_r 40,000). Two polypeptides (M_r 27,000 and 70,000) dominated residual protein synthesis in severe ischemia. The changes in protein synthesis induced by different grades of ischemia most likely comprise a variation of the so-called “heat shock” or “stress” response found in all eukaryotic cells subjected to adverse conditions. Since heat shock genes are known to confer partial protection against anoxia and a variety of other noxious insults, their induction may be a factor in limiting the extent of ischemic tissue damage.