1,6-Diaminohexane contributes to the hexamethylene bisacetamide-induced erythroid differentiation pathway by stimulating Ca2+ release from inositol 1,4,5-trisphosphate-sensitive stores and promoting Ca2+ influx.
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 inositol 1,4,5-trisphosphate (IP(3)) receptors, as we observed similar Ca(2+) release characteristics and heparin sensitivity of DAH and IP(3) 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.
Rajagopalan
Vanishree
V
Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA.
Blankenship
Jim
J
Thomas
David W
DW
D000081:Acetamides / Q000494:pharmacology*; D000107:Acetylation; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003959:Diamines / Q000494:pharmacology*; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology
D000081:Acetamides; D001896:Boron Compounds; D003959:Diamines; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; C109986:2-aminoethoxydiphenyl borate; C014026:hexamethylene bisacetamide; D002118:Calcium; C007297:1,6-diaminohexane