title: Decreased sulfation of cellular chondroitin sulfate in response to activators of protein kinase C.
abstract: The sulfation of cellular chondroitin sulfate in human promyelocytic leukemia HL60 cells was inhibited by a number of phorbol diesters, which concurrently induced differentiation into monocytic cells. Inhibition was dependent on concentration, and was 90% complete at 10 nM 12-0-tetradecanoylphorbol-13-acetate (TPA), the most active ester. Maximal effects were seen within 2-4 hours following initiation of treatment. The degree of inhibition observed correlated well with the ability of the esters to induce differentiation, and with their reported affinity for a "receptor", identified as protein kinase C associated with certain lipids. Chondroitin sulfation was also inhibited in cells treated with sn-1,2-dioctanoylglycerol, a lipid which is considered to be an endogenous activator of protein kinase C. Our findings therefore indicate that monocytic differentiation of HL60 cells occurs subsequent to reduced glycosaminoglycan sulfation via activation of the calcium-activated, phospholipid-dependent protein kinase.
authors.forename: D L
authors.initials: DL
authors.lastname: Carson
authors.forename: C S
authors.initials: CS
authors.lastname: Baxter
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002807:Chondroitin / Q000031:analogs & derivatives*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D004224:Diterpenes; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D002807:Chondroitin; D002809:Chondroitin Sulfates; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate