Heparan sulfate and control of endothelial cell proliferation: increased synthesis during the S phase of the cell cycle and inhibition of thymidine incorporation induced by ortho-nitrophenyl-beta-D-xylose.
The effect of xylosides on the synthesis of [35S]-sulfated glycosaminoglycans by endothelial cells in culture was investigated. Ortho-nitrophenyl-beta-D-xylose (10(-3)M) produces a dramatic enhancement on the synthesis of heparan sulfate and chondroitin sulfate secreted to the medium (20- and 100-fold, respectively). Para-nitrophenylxyloside, at the same concentration, produces an enhancement of only 37- and 3-fold of chondroitin sulfate and heparan sulfate, respectively. These differences of action seem to be related with the higher lipophilic character of ortho-nitrophenyl-xyloside. A lower enhancement of the synthesis of the two glycosaminoglycans is also observed with 2-naphtol beta-D-xylose and cis/trans-decahydro-2-naphtol beta-D-xylose. Besides stimulating the synthesis, O-nitrophenyl-beta-D-xylose as PMA [J. Cell. Biochem. 70 (1998) 563] also inhibits [3H]-thymidine incorporation by quiescent endothelial cells stimulated for growth by fetal calf serum (FCS). The combination of xylosides with PMA produced some cumulative effect. PMA stimulates the synthesis of heparan sulfate mainly at G1 phase whereas the highest enhancement of synthesis produced by the xylosides is in the S phase of the endothelial cell cycle.
Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Três de Maio, 4 degrees andar, 100, Vila Clementino, CEP 04044-020, São Paulo, SP, Brazil.
Claudia R
CR
Moreira
Carla C
CC
Lopes
Iolanda M
IM
Cuccovia
Marimélia A
MA
Porcionatto
Carl P
CP
Dietrich
Helena B
HB
Nader
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006497:Heparan Sulfate / Q000494:pharmacology*; D011817:Rabbits; D016196:S Phase / Q000187:drug effects*; D013936:Thymidine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014994:Xylose / Q000031:analogs & derivatives / Q000494:pharmacology*
D006497:Heparan Sulfate; D013936:Thymidine; D014994:Xylose; C490194:nitrophenylxylose