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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0280.
Submitted January 30, 2002
Accepted April 13, 2002
Hemin induces neuroglobin expression in neural cells
Yonghua Zhu, Yunjuan Sun, Kunlin Jin, and David A Greenberg*
Buck Institute for Age Research, Novato, CA, USA
* Corresponding author; email: dgreenberg{at}buckinstitute.org.
Neuroglobin is a newly identified vertebrate globin that binds O2 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- and time-dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and protein levels occurring with 50 µM hemin and at 8-24 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-Br-cGMP, and was accompanied by a >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 (MEK) 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 two signal transduction pathways.
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