Basal and induced nitric oxide and cGMP productions are decreased in senescent cultured rat articular chondrocytes.
The effects of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharide (LPS) on the productions of nitric oxide (NO) and cGMP by cultured articular chondrocyte (AC) monolayers from 1-, 8- and 18-month old male Wistar rats were studied. It was found that basal NO and cGMP productions decrease with the age of animals. The productions were more than 2-fold greater in cells from 1-month old rats then in cells from older animals. IL-1, TNF-alpha, and LPS stimulated all three types of cells to produce NO and cGMP in a time- and concentration-dependent manner. Although the cells from young animals produced more NO per microg DNA, the older counterparts were more sensitive to these agents since they produced more NO upon stimulation then the corresponding non-stimulated controls. At the concentration of 10(-3) M, the nitric oxide synthase (NOS) inhibitor, Ng-monomethyl-L-arginine (L-NMA), blocked, although incompletely, both the basal and stimulated NO and cGMP productions in cells from the 1 and 8-month old rats and only induced productions in 18-month old counterparts. These results show a decreased capacity of unstimulated- and stimulated-AC from old rats to produce NO and cGMP in culture, which may affect the ageing cells in some yet unknown way.
Khatib
A M
AM
INSERM Unité 349, Hôpital Lariboisière, Paris, France.
Siegfried
G
G
Messai
H
H
Quintero
M
M
Barbara
A
A
Mitrovic
R D
RD
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002358:Cartilage, Articular; D002478:Cells, Cultured; D016922:Cellular Senescence; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006152:Cyclic GMP