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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0280.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2494-2498
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Hemin induces neuroglobin expression in neural cells
Yonghua Zhu,
Yunjuan Sun,
Kunlin Jin, and
David A. Greenberg
From the Buck Institute for Age Research, Novato, CA.
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 dependent and time
dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and protein levels occurring with 50 µM 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.
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