Hydroxyurea induces fetal hemoglobin expression by activating cAMP signaling pathways in a cAMP- and cGMP-dependent manner

Hdl Handle:
http://hdl.handle.net/10675.2/940
Title:
Hydroxyurea induces fetal hemoglobin expression by activating cAMP signaling pathways in a cAMP- and cGMP-dependent manner
Authors:
Ikuta, Tohru; Gutsaeva, Diana R.; Parkerson, James B.; Yerigenahally, Shobha D; Head, C. Alvin
Abstract:
Here we show that hydroxyurea (HU) induces fetal hemoglobin (HbF) expression by activating the cAMP pathway through two independent mechanisms. Although HU increased both cAMP and cGMP levels in CD34+-derived erythroblasts, only the cAMP pathway was found to be activated. However, HU-induced HbF expression was affected by the activities of both adenylate cyclase (AC) and soluble guanylate cyclase (sGC). HU decreased the expression of cGMP-inhibitable phosphodiesterase (PDE) 3B in a sGC-dependent manner, resulting in activation of the cAMP pathway. Second, HU induced the expression of cyclooxygenase-1 (COX-1) and increased the production of prostaglandin E2 (PGE2), which resulted in activation of the cAMP signaling pathway through AC. HU therapy elevated plasma PGE2 levels in sickle cell patients. These results demonstrate that HU induces HbF expression by activating the cAMP pathway via dual signaling mechanisms.
Publisher:
American Society of Hematology
Issue Date:
Dec-2010
URI:
http://hdl.handle.net/10675.2/940
Language:
en_US
Series/Report no.:
ASH;2010-H02
Appears in Collections:
Department of Anesthesiology and Perioperative Medicine: Faculty Research and Presentaions

Full metadata record

DC FieldValue Language
dc.contributor.authorIkuta, Tohru-
dc.contributor.authorGutsaeva, Diana R.-
dc.contributor.authorParkerson, James B.-
dc.contributor.authorYerigenahally, Shobha D-
dc.contributor.authorHead, C. Alvin-
dc.date.accessioned2013-02-21T22:53:17Z-
dc.date.available2013-02-21T22:53:17Z-
dc.date.issued2010-12-
dc.identifier.urihttp://hdl.handle.net/10675.2/940-
dc.description.abstractHere we show that hydroxyurea (HU) induces fetal hemoglobin (HbF) expression by activating the cAMP pathway through two independent mechanisms. Although HU increased both cAMP and cGMP levels in CD34+-derived erythroblasts, only the cAMP pathway was found to be activated. However, HU-induced HbF expression was affected by the activities of both adenylate cyclase (AC) and soluble guanylate cyclase (sGC). HU decreased the expression of cGMP-inhibitable phosphodiesterase (PDE) 3B in a sGC-dependent manner, resulting in activation of the cAMP pathway. Second, HU induced the expression of cyclooxygenase-1 (COX-1) and increased the production of prostaglandin E2 (PGE2), which resulted in activation of the cAMP signaling pathway through AC. HU therapy elevated plasma PGE2 levels in sickle cell patients. These results demonstrate that HU induces HbF expression by activating the cAMP pathway via dual signaling mechanisms.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society of Hematologyen_US
dc.relation.ispartofseriesASH;2010-H02-
dc.subjectSickle cell diseaseen_US
dc.subjectHydroxyureaen_US
dc.subjectcAMPen_US
dc.subjectFetal hemoglobinen_US
dc.titleHydroxyurea induces fetal hemoglobin expression by activating cAMP signaling pathways in a cAMP- and cGMP-dependent manneren_US
dc.contributor.corporatenameDepartment of Anesthesiology and Perioperative Medicineen_US
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