MAP kinase activation by mu opioid receptor in cord blood CD34+CD38- cells

Galit Rozenfeld-Granot, Amos Toren, Ninette Amariglio, Arnon Nagler, Ester Rosenthal, Miriam Biniaminov, Frida Brok-Simoni, Gideon Rechavi

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Objective. Opioid receptor expression and function traditionally have been studied in neuronal cells and recently in mature lymphoid cells; however, little is known about their possible functions in hematopoietic stem cells (CD34+ cells). We studied the expression of the mu receptor on CD34+ cells and assessed the signal transduction cascade it induces. Materials and Methods. Mu-receptor expression on cord blood (CB) and peripheral blood (PB) CD34+ cells was studied by microarrays, immunostaining, and fluorescence-activated cell sorting analysis. Signal transduction by the mu receptor was studied through Western blots and kinase assay of enkephalin-activated CB CD34+ cells. Apoptotic, differentiation, and proliferation responses following mu-receptor activations were studied by annexin V assay and inverted microscopy. Results. A prominent difference in gene expression, in favor of CB compared to PB CD34+ cells, was observed in the mu-receptor gene. This receptor was mainly expressed on the CB CD34+CD38- subpopulation. A MAP kinase signal transduction cascade was shown to be induced through activation of this receptor by enkephalin or morphine. Conclusions. We showed for the first time that the mu receptor is expressed on immature CB stem cells and that its activation by enkephalin or morphine induces a MAP kinase signal transduction cascade. Because the MAP kinase cascade is known to elicit proliferation and differentiation responses, these findings suggest a possible role of endogenous enkephalins in hematopoietic stem cell proliferation and differentiation and may lead to therapeutic applications of opiates in CB stem cell expansion and neuronal differentiation.

Original languageEnglish
Pages (from-to)473-480
Number of pages8
JournalExperimental Hematology
Issue number5
StatePublished - May 2002
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Rich Foundation and by the Arison Dorsman Family. G. Rechavi holds the Gregorio and Dora Shapiro Chair in hematologic malignancies at the Sackler School of Medicine. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Galit Rozenfeld, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.


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