Na+/H+ antiporter gene expression increases during retinoic acid‐induced granulocytic differentiation of HL60 cells

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Abstract
During differentiation of human leukemic HL60 cells into granulocytes, sustained increases in intracellular pH and Na+/H+ antiporter activity have been observed. In the present study we report that retinoic acid (RA)‐induced granulocytic differentiation of HL60 cells causes an ∼18‐fold increase in the steady‐state mRNA levels for the Na+/H+ antiporter. This was due to an increase in the rate of Na+/H+ antiporter gene transcription as measured by nuclear run‐on analysis. Antiporter protein synthesis increased by seven‐fold during RA‐induced granulocytic differentiation of HL60 cells as measured by immunoprecipitation of 35S‐methionine‐labeled proteins with the RP1‐c28 Na+/H+ antiporter antibody. No increase in antiporter mRNA was observed in response to etretinate, an analogue of retinoic acid, which did not induce differentiation. Thus, Na+/H+ antiporter gene expression is associated with RA‐induced granulocytic differentiation of HL60 cells. The present findings and our previous data (Rao et al., 1991) demonstrate that Na+/H+ antiporter gene expression is a generalized feature of HL60 cell differentiation.