N-Methyl-L-serine stimulates hyaluronan production in human skin fibroblasts.
We examined the effects of N-methyl-L-serine (NMS), an amino acid derivative, on hyaluronan (HA) synthesis in human skin fibroblasts. NMS (1-10 mM), but not L-serine, stimulated the incorporation of [(3)H]glucosamine into HA dose-dependently, with a maximum stimulation of 1.5-fold compared to the control. The effect of NMS was specific for HA production, because there was no change in sulfated glycosaminoglycan formation. Neither the N-methyl derivatives of L-glycine or L-alanine, nor N-methyl-D-serine, could stimulate HA synthesis, indicating that the beta-hydroxyl group and the L-configuration were essential for the activity. Gel filtration of the products showed that NMS stimulated the production of high-molecular-mass HA (>10(6) D) without affecting the production of low-molecular-mass HA. NMS required 24 h to stimulate HA production, and when fibroblasts were pretreated for 10-24 h with NMS (1-10 mM), membrane-associated HA synthase activity was increased dose-dependently. Thus, a second messenger is likely to be involved in the stimulation of HA production by NMS.
Sakai
S
S
Basic Research Laboratory, Kanebo Ltd., Odawara, Japan.
Sayo
T
T
Kodama
S
S
Inoue
S
S
D000596:Amino Acids / Q000494:pharmacology; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000032:analysis / Q000096:biosynthesis*; D008565:Membrane Proteins; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors; D014166:Transferases; D029867:Xenopus Proteins
D000596:Amino Acids; D008565:Membrane Proteins; D029867:Xenopus Proteins; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases