Zhu Yonghua, Sun Yunjuan, Jin Kunlin, Greenberg David A
Buck Institute for Age Research, Novato, CA 94945, USA.
Blood. 2002 Oct 1;100(7):2494-8. doi: 10.1182/blood-2002-01-0280.
Neuroglobin is a newly identified vertebrate globin that binds O(2) and is expressed in cerebral neurons. We found recently that neuronal expression of neuroglobin is stimulated by hypoxia and ischemia and protects neurons from hypoxic injury. Here we report that, like hemoglobin and myoglobin, neuroglobin expression can also be induced by hemin. Induction was concentration dependent and time dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and protein levels occurring with 50 microM hemin and at 8 to 24 hours. The inductive effect of hemin was attenuated by the protein kinase G inhibitor KT5823 and the soluble guanylate cyclase inhibitor LY83583, was mimicked by treatment with 8-bromo-cyclic guanosine 3',5'-monophosphate, and was accompanied by a greater than 10-fold increase in cGMP levels, suggesting that it is mediated through protein kinase G and soluble guanylate cyclase. In contrast, hypoxic induction of neuroglobin was blocked by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059, indicating that hemin and hypoxia regulate neuroglobin expression by different mechanisms. These results provide evidence for regulation of neuroglobin expression by at least 2 signal transduction pathways.
神经球蛋白是一种新发现的脊椎动物球蛋白，可结合氧气并在脑神经元中表达。我们最近发现，神经球蛋白的神经元表达受缺氧和缺血刺激，并能保护神经元免受缺氧损伤。在此我们报告，与血红蛋白和肌红蛋白一样，神经球蛋白的表达也可被血红素诱导。诱导呈浓度依赖性和时间依赖性，在50微摩尔血红素作用下，8至24小时时神经球蛋白mRNA和蛋白质水平出现最大（约4倍）增加。蛋白激酶G抑制剂KT5823和可溶性鸟苷酸环化酶抑制剂LY83583可减弱血红素的诱导作用，用8-溴环鸟苷3',5'-单磷酸处理可模拟该作用，且伴随cGMP水平增加超过10倍，表明其通过蛋白激酶G和可溶性鸟苷酸环化酶介导。相比之下，丝裂原活化蛋白激酶/细胞外信号调节激酶激酶抑制剂PD98059可阻断神经球蛋白的缺氧诱导，表明血红素和缺氧通过不同机制调节神经球蛋白表达。这些结果为至少两种信号转导途径调节神经球蛋白表达提供了证据。
