1,6-Diaminohexane contributes to the hexamethylene bisacetamide-induced erythroid differentiation pathway by stimulating Ca~(2+) release from inositol 1,4,5-trisphosphate-sensitive stores and promoting Ca~(2+) influx

摘要

Hexamethylene bisacetamide (HMBA) stimulates Ca~(2+) signals in murine erythroleukemia (MEL) cells serving as an important component of the HMBA-induced pathway that promotes differentiation to the erythroid phenotype. We observed that 1,6-diaminohexane (DAH) triggered a more rapid and robust increase in MEL cell Ca~(2+) levels compared to HMBA and the monodeacetylated N-acetyl-1,6-diaminohexane (NADAH), and that polyamine deacetylase inhibition completely abolished the ability of HMBA and NADAH to induce Ca~(2+) signals in MEL cells. Our work indicates that DAH mediates Ca~(2+) signal propagation via its ability to activate inositol1,4,5-trisphosphate (IP3) receptors, as we observed similar Ca~(2+) release characteristics and heparin sensitivity of DAH and IP3 in permeabilized MEL cells. Finally, we observed that the DAH-induced Ca~(2+) release pathway robustly coupled to a Ca~(2+)influx pathway that could be distinguished from thapsigargin-induced Ca~(2+) influx by its unusual insensitivity to 2-aminoethoxydiphenyl borate.