RAPID INDUCTION OF HEME OXYGENASE-1 MESSENGER-RNA AND PROTEIN BY HYPERTHERMIA IN RAT-BRAIN - HEME OXYGENASE-2 IS NOT A HEAT-SHOCK PROTEIN
RAPID INDUCTION OF HEME OXYGENASE-1 MESSENGER-RNA AND PROTEIN BY HYPERTHERMIA IN RAT-BRAIN - HEME OXYGENASE-2 IS NOT A HEAT-SHOCK PROTEIN
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DOI：
10.1073/pnas.88.12.5364
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
MAINES, MD
中科院分区：
文献类型：
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作者：
EWING, JF;MAINES, MD
血红素加氧酶(血红素，氢供体：氧氧化还原酶，EC 1.14.“.3)同工酶HO-1和HO-2的催化活性允许产生胆汁色素的生理异构体。反过来，胆色素胆绿素和胆红素在生物系统中是有效的抗氧化剂。在大鼠的大脑中，我们只确定了血红素加氧酶的HO-1同工酶是一种热休克蛋白，并将高热定义为导致大脑HO-1蛋白增加的刺激。雄性大鼠暴露在42摄氏度的环境中20分钟，脑内1.8千碱基的HO-1mRNA迅速而显著增加。具体地说，脑HO-1mRNA在治疗后1h内增加了33倍，并持续到至少6h。相反，两个HO-2同源转录本(1.3和1.9kb)对热休克没有反应；当在热疗后1、6或24小时测量时，这两个信息的比率和水平都与对照组没有差异。Western免疫印迹和RIA检测显示，诱导1.8kb的HO-1mRNA可导致高温后6h HO-1蛋白的表达显著增加。大鼠脑免疫细胞化学显示HO-1样蛋白仅在特定脑区的神经元中呈离散分布。热休克6小时后，在小脑浦肯野细胞和大脑导水管内的上皮细胞中均观察到HO-1样蛋白的显著增加。我们认为，HO-1蛋白的增加，从而增强了形成胆汁色素的能力，代表了神经元对热休克应激的防御机制。
Catalytic activity of heme oxygenase (heme, hydrogen-donor:oxygen oxidoreductase, EC 1.14.".3) isozymes, HO-1 and HO-2, permits production of physiologic isomers of bile pigments. In turn, bile pigments biliverdin and bilirubin are effective antioxidants in biological systems. In the rat brain we have identified only the HO-1 isozyme of heme oxygenase as a heat shock protein and defined hyperthermia as a stimulus that causes an increase in brain HO-1 protein. Exposure of male rats to 42-degrees-C for 20 min caused a rapid and marked increase in brain 1.8-kilobase HO-1 mRNA. Specifically, a 33-fold increase in brain HO-1 mRNA was observed within 1 h and sustained for at least 6 h posttreatment. In contrast, the two HO-2 homologous transcripts (1.3 and 1.9 kilobases) did not respond to heat shock; neither the ratio nor the level of the two messages differed from that of the control when measured either at 1, 6, or 24 h after hyperthermia. The induction of a 1.8-kilobase HO-1 mRNA resulted in a pronounced increase in HO-1 protein 6 h after hyperthermia, as detected by both Western immunoblot and RIA. Immunocytochemistry of rat brain showed discrete localization of HO-1-like protein only in neurons of select brain regions. Six hours after heat shock, an intense increase in HO-1-like protein was observed in both Purkinje cells of the cerebellum and epithelial cells lining the cerebral aqueduct of the brain. We suggest that the increase in HO-1 protein, hence increased capacity to form bile pigments, represents a neuronal defense mechanism against heat shock stress.