title: Expression of (Pro)renin Receptor During Rapamycin-Induced Erythropoiesis in K562 Erythroleukemia Cells and Its Possible Dual Actions on Erythropoiesis.
abstract: (Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is expressed in erythroblastic cells. (P)RR has multiple biological actions: prorenin activation, stimulation of the intracellular signaling including extracellular signal-regulated kinases, and functional complex formation with vacuolar H+-ATPase (v-ATPase). However, the functional implication of (P)RR in erythroblast cells has not been clarified. The aim of the present study was to clarify changes of (P)RR expression during erythropoiesis and a role of (P)RR in the heme synthesis. (P)RR expression was studied during rapamycin-induced erythropoiesis in a human erythroleukemia cell line, K562. Treatment with rapamycin (100 nM) for 48 hours significantly increased %number of hemoglobin-producing cells, γ-globin mRNA levels, erythroid specific 5-aminolevulinate synthase (ALAS2) mRNA levels, and heme content in K562 cells. Both (P)RR protein and mRNA levels increased about 1.4-fold during rapamycin-induced erythropoiesis. Suppression of (P)RR expression by (P)RR-specific small interference RNA increased ALAS2 mRNA levels about 1.6-fold in K562 cells, compared to control using scramble RNA, suggesting that (P)RR may down-regulate ALAS2 expression. By contrast, treatment with bafilomycin A1, an inhibitor of v-ATPase, decreased greatly % number of hemoglobin-producing cells and heme content in K562 cells, indicating that the v-ATPase function is essential for hemoglobinization and erythropoiesis. Treatment with bafilomycin A1 increased (P)RR protein and mRNA levels. In conclusion, we propose that (P)RR has dual actions on erythropoiesis: the promotion of erythropoiesis via v-ATPase function and the down-regulation of ALAS2 mRNA expression. Thus, (P)RR may contribute to the homeostatic control of erythropoiesis.
authors.affiliation: Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine.
authors.forename: Kiriko
authors.initials: K
authors.lastname: Kaneko
authors.forename: Koji
authors.initials: K
authors.lastname: Ohba
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Totsune
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Furuyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D006454:Hemoglobins; D018942:Macrolides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C040929:bafilomycin A1; D000624:5-Aminolevulinate Synthetase; C480079:ALAS2 protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000093342:Prorenin Receptor