Marton L S, Wang X, Kowalczuk A, Zhang Z D, Windmeyer E, Macdonald R L
Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2405-13. doi: 10.1152/ajpheart.2000.279.5.H2405.
Ferrous Hb contributes to cerebral vasospasm after subarachnoid hemorrhage, although the mechanisms involved are uncertain. The hypothesis that cytotoxic effects of ferrous Hb on smooth muscle cells contribute to vasospasm was assessed. Cultured rat basilar artery smooth muscle cells were exposed to pure Hb, dog erythrocyte hemolysate, or Hb breakdown products; and heme oxygenase (HO-1 and HO-2) and ferritin mRNA and protein were measured. Cytotoxicity was assessed by lactate dehydrogenase release and fluorescence assays. Pure Hb or hemolysate caused dose- and time-dependent increases in HO-1 mRNA and protein. Hemin was the component of Hb that increased HO-1 mRNA. Cycloheximide inhibited the increase in HO-1 mRNA in response to hemin. Ferritin protein heavy chain but not mRNA increased upon exposure of cells to Hb. Hemin and ferric but not ferrous Hb were toxic to smooth muscle cells. Toxicity was increased by exposure to Hb plus tin protoporphyrin IX. In conclusion, exposure of smooth muscle cells to Hb induces HO-1 mRNA and protein through pathways that involve new protein synthesis. Hemin is the component of Hb that induces HO-1. Hemin and ferric but not ferrous Hb are toxic.
亚铁血红蛋白会导致蛛网膜下腔出血后的脑血管痉挛，尽管其中涉及的机制尚不清楚。本研究评估了亚铁血红蛋白对平滑肌细胞的细胞毒性作用导致血管痉挛的假说。将培养的大鼠基底动脉平滑肌细胞暴露于纯血红蛋白、犬红细胞溶血产物或血红蛋白分解产物中，检测血红素加氧酶（HO-1和HO-2）以及铁蛋白的mRNA和蛋白水平。通过乳酸脱氢酶释放和荧光测定法评估细胞毒性。纯血红蛋白或溶血产物可引起HO-1 mRNA和蛋白呈剂量和时间依赖性增加。血红素是血红蛋白中增加HO-1 mRNA的成分。放线菌酮可抑制细胞对血红素反应时HO-1 mRNA的增加。细胞暴露于血红蛋白后，铁蛋白重链蛋白增加，但其mRNA未增加。血红素和高铁血红蛋白而非亚铁血红蛋白对平滑肌细胞有毒性。暴露于血红蛋白加锡原卟啉IX会增加毒性。总之，平滑肌细胞暴露于血红蛋白会通过涉及新蛋白质合成的途径诱导HO-1 mRNA和蛋白。血红素是血红蛋白中诱导HO-1的成分。血红素和高铁血红蛋白而非亚铁血红蛋白具有毒性。
