Retinoic acid-induced granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by downregulation of autonomous generation of inositol lipid-derived second messengers

Journal Article · Thu Aug 15 00:00:00 EDT 1991 · Blood (Journal of Hematology); (United States)

OSTI ID:6203626

Porfiri, E; Hoffbrand, A V; Wickremasinghe, R G ^[1]

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1. Royal Free Hospital School of Medicine (London)

Inositol phosphates (InsPs) and diacyglycerol (DAG) are second messengers derived via the breakdown of inositol phospholipids, and which play important signalling roles in the regulation of proliferation of some cell types. The authors have studied the operation of this pathway during the early stages of retionic acid (RA)-induced granulocytic differentiation of HL60 myeloid leukemia cells. The autonomous breakdown of inositol lipids that occurred in HL60 cells labeled with (3H) inositol was completely abolished following 48 hours of RA treatment. The rate of influx of 45Ca2+ was also significantly decreased at 48 hours, consistent with the role of inositol lipid-derived second messengers in regulating Ca2+ entry into cells. The downregulation of inositol lipid metabolism clearly preceded the onset of reduced proliferation induced by RA treatment, and was therefore not a consequence of decreased cell growth. The generation of InsPs in RA-treated cells was reactivated by the fluoroaluminate ion, a direct activator of guanine nucleotide-binding protein(s) (G proteins) that regulate the inositol lipid signalling pathway. Subtle alterations to a regulatory mechanism may therefore mediate the RA-induced downregulation of this pathway. The data are consistent with the hypothesis that the autonomous generation of inositol lipid-derived second messengers may contribute to the continuous proliferation of HL60 cells, and that the RA-induced downregulation of this pathway may, in turn, play a role in signalling the cessation of proliferation that preceedes granulocytic differentiation.

• OSTI ID: 6203626
• Journal Information: Blood (Journal of Hematology); (United States), Vol. 78:4; ISSN 0006-4971
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
PHOSPHOLIPIDS
BIOSYNTHESIS
RETINOIC ACID
BIOCHEMICAL REACTION KINETICS
TUMOR CELLS
CELL DIFFERENTIATION
BIOLOGICAL PATHWAYS
CALCIUM 45
CELL DIVISION
FLUORINE
HYDROLYSIS
HYDROXYUREA
INHIBITION
LEUKEMIA
LEUKOCYTES
MAN
PHOSPHODIESTERASES
TRACER TECHNIQUES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
AMIDES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM ISOTOPES
CARBOXYLIC ACID ESTERS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DISEASES
ELEMENTS
ENZYMES
ESTERASES
ESTERS
EVEN-ODD NUCLEI
HALOGENS
HYDROLASES
HYDROXY COMPOUNDS
IMMUNE SYSTEM DISEASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
LYSIS
MAMMALS
MATERIALS
NEOPLASMS
NONMETALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PRIMATES
RADIOISOTOPES
REACTION KINETICS
SOLVOLYSIS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques