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

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.