Oxidative stress-induced poly(ADP-ribosyl)ation in chick limb bud-derived chondrocytes.
Oxidative stress has been implicated in the pathogenesis of various diseases affecting chondrogenesis or the function of articular cartilage. DNA damage caused by oxidative stress may trigger the activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) which may contribute to tissue injury. We aimed at investigating the effects of peroxynitrite (100-600 microM) and hydrogen peroxide (0.1-4 mM) on PARP activation and extracellular matrix production of high density micromass cultures (HDC) prepared from chick limb bud mesenchymal cells. We found that both oxidative species strongly inhibited matrix formation of HDCs treated on day 2 but not on day 5. The PARP inhibitor 3-aminobenzamide (3-AB) stimulated matrix production in non-stressed cells and prevented suppressed matrix production in oxidatively stressed cells. Both hydrogen peroxide and peroxynitrite induced PARP activation and poly(ADP-ribose) accumulation. Decreased proliferation, viability and NAD+ content were not or only slightly improved by 3-AB, indicating that 3-AB directly affects matrix formation. In conclusion, oxidative stress stimulates poly(ADP-ribose) metabolism and inhibits extracellular matrix production of HDCs in a PARP-dependent manner. Our findings may have implications for potential therapeutic approaches aimed at restoring the matrix production capacity of chondrogenic cells.
Zákány
Róza
R
Department of Anatomy, Histology and Embryology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Bakondi
Edina
E
Juhász
Tamás
T
Matta
Csaba
C
Szíjgyártó
Zsolt
Z
Erdélyi
Katalin
K
Szabó
Eva
E
Módis
László
L
Virág
László
L
Gergely
Pál
P
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002356:Cartilage / Q000196:embryology* / Q000201:enzymology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002642:Chick Embryo; D019902:Chondrocytes / Q000201:enzymology* / Q000648:ultrastructure; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018878:Limb Buds; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism*
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D030421:Peroxynitrous Acid; C025160:3-aminobenzamide; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases