Jacewicz M, Kiessling M, Pulsinelli W A
J Cereb Blood Flow Metab. 1986 Jun;6(3):263-72. doi: 10.1038/jcbfm.1986.48.
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 (Mr 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 (Mr 27,000, 34,000, 73,000, 79,000, and actin) including two new polypeptides (Mr 55,000 and 70,000). Severe ischemia (CBF = 15-25 ml 100 g-1 min-1) caused the isoelectric modification of several proteins (Mr 44,000, 55,000, and 70,000) and induced synthesis of another protein (Mr 40,000). Two polypeptides (Mr 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.
通过闭塞大鼠右侧颈总动脉和大脑中动脉制造局部缺血模型，研究大鼠皮质中蛋白质合成的区域模式。在缺血2小时时，通过向皮质内注射[3H]亮氨酸、[3H]异亮氨酸和[3H]脯氨酸的混合物对蛋白质进行脉冲标记。通过二维凝胶荧光成像分析新合成的蛋白质，并将结果与用[14C]碘代安替比林作为示踪剂测量的局部脑血流量（CBF）相关联。小幅度的血流量减少（CBF = 50 - 80 ml·100g-1·min-1）伴随着许多蛋白质合成的适度抑制以及一种蛋白质（分子量27,000）的显著增加。随着血流量进一步减少（CBF = 40 ml·100g-1·min-1），合成仅限于一小部分蛋白质（分子量27,000、34,000、73,000、79,000和肌动蛋白），包括两种新的多肽（分子量55,000和70,000）。严重缺血（CBF = 15 - 25 ml·100g-1·min-1）导致几种蛋白质（分子量44,000、55,000和70,000）的等电点改变，并诱导另一种蛋白质（分子量40,000）的合成。两种多肽（分子量27,000和70,000）在严重缺血时主导了残留的蛋白质合成。不同程度缺血诱导的蛋白质合成变化很可能是所有遭受不利条件的真核细胞中发现的所谓“热休克”或“应激”反应的一种变体。由于已知热休克基因可提供对缺氧和多种其他有害损伤的部分保护，它们的诱导可能是限制缺血组织损伤程度的一个因素。
