Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance: Prolyl hydroxylase as a possible target

M. Cao, A. Westerhausen-Larson, C. Niyibizi, K. Kavalkovich, H. I. Georgescu, C. F. Rizzo, P. A. Hebda, M. Stefanovic-Racic, C. H. Evans

Research output: Contribution to journalArticle

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Abstract

The addition of human recombinant interleukin-1β (IL-1β) to cultures of lapine articular chondrocytes provoked the synthesis of large amounts of NO and reduced the production of type-II collagen. N(G)-Monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, strongly suppressed the production of NO and partially relieved the inhibition of collagen synthesis in response to IL-1β. The NO donor S-nitrosoacetylpenicillamine (SNAP), on the other hand, inhibited collagen production. IL-1 lowered the abundance of Col2A1 mRNA in an NO-independent manner. Collectively, these data indicate that IL-1 suppresses collagen synthesis at two levels: a pretranslational level which is NO-independent, and a translational or post-translational level which is NO-mediated. These effects are presumably specific as L-NMA and SNAP had no effect on total protein synthesis or on the distribution of newly synthesized proteins between the cellular and extracellular compartments. Prolyl hydroxylase is an important enzyme in the post-translational processing of collagen, and its regulation and cofactor requirements suggest possible sensitivity to NO. Extracts of cells treated with IL-1 or SNAP had lower prolyl hydroxylase activity, and L-NMA was partially able to reverse the effects of IL-1. These data suggest that prolyl hydroxylase might indeed be a target for NO. Because under-hydroxylated collagen monomers fail to anneal into stable triple helices, they are degraded intracellularly. Inhibition of prolyl hydroxylase by NO might thus account for the suppressive effect of this radical on collagen synthesis.

Original languageEnglish (US)
Pages (from-to)305-310
Number of pages6
JournalBiochemical Journal
Volume324
Issue number1
DOIs
StatePublished - May 15 1997

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Prolyl Hydroxylases
Collagen Type II
Interleukin-1
Nitric Oxide
Collagen
Messenger RNA
Chondrocytes
Cell Extracts
Nitric Oxide Synthase
Arginine
Proteins
Joints
Monomers
Enzymes
Processing

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cao, M. ; Westerhausen-Larson, A. ; Niyibizi, C. ; Kavalkovich, K. ; Georgescu, H. I. ; Rizzo, C. F. ; Hebda, P. A. ; Stefanovic-Racic, M. ; Evans, C. H. / Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance : Prolyl hydroxylase as a possible target. In: Biochemical Journal. 1997 ; Vol. 324, No. 1. pp. 305-310.
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title = "Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance: Prolyl hydroxylase as a possible target",
abstract = "The addition of human recombinant interleukin-1β (IL-1β) to cultures of lapine articular chondrocytes provoked the synthesis of large amounts of NO and reduced the production of type-II collagen. N(G)-Monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, strongly suppressed the production of NO and partially relieved the inhibition of collagen synthesis in response to IL-1β. The NO donor S-nitrosoacetylpenicillamine (SNAP), on the other hand, inhibited collagen production. IL-1 lowered the abundance of Col2A1 mRNA in an NO-independent manner. Collectively, these data indicate that IL-1 suppresses collagen synthesis at two levels: a pretranslational level which is NO-independent, and a translational or post-translational level which is NO-mediated. These effects are presumably specific as L-NMA and SNAP had no effect on total protein synthesis or on the distribution of newly synthesized proteins between the cellular and extracellular compartments. Prolyl hydroxylase is an important enzyme in the post-translational processing of collagen, and its regulation and cofactor requirements suggest possible sensitivity to NO. Extracts of cells treated with IL-1 or SNAP had lower prolyl hydroxylase activity, and L-NMA was partially able to reverse the effects of IL-1. These data suggest that prolyl hydroxylase might indeed be a target for NO. Because under-hydroxylated collagen monomers fail to anneal into stable triple helices, they are degraded intracellularly. Inhibition of prolyl hydroxylase by NO might thus account for the suppressive effect of this radical on collagen synthesis.",
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Cao, M, Westerhausen-Larson, A, Niyibizi, C, Kavalkovich, K, Georgescu, HI, Rizzo, CF, Hebda, PA, Stefanovic-Racic, M & Evans, CH 1997, 'Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance: Prolyl hydroxylase as a possible target', Biochemical Journal, vol. 324, no. 1, pp. 305-310. https://doi.org/10.1042/bj3240305

Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance : Prolyl hydroxylase as a possible target. / Cao, M.; Westerhausen-Larson, A.; Niyibizi, C.; Kavalkovich, K.; Georgescu, H. I.; Rizzo, C. F.; Hebda, P. A.; Stefanovic-Racic, M.; Evans, C. H.

In: Biochemical Journal, Vol. 324, No. 1, 15.05.1997, p. 305-310.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance

T2 - Prolyl hydroxylase as a possible target

AU - Cao, M.

AU - Westerhausen-Larson, A.

AU - Niyibizi, C.

AU - Kavalkovich, K.

AU - Georgescu, H. I.

AU - Rizzo, C. F.

AU - Hebda, P. A.

AU - Stefanovic-Racic, M.

AU - Evans, C. H.

PY - 1997/5/15

Y1 - 1997/5/15

N2 - The addition of human recombinant interleukin-1β (IL-1β) to cultures of lapine articular chondrocytes provoked the synthesis of large amounts of NO and reduced the production of type-II collagen. N(G)-Monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, strongly suppressed the production of NO and partially relieved the inhibition of collagen synthesis in response to IL-1β. The NO donor S-nitrosoacetylpenicillamine (SNAP), on the other hand, inhibited collagen production. IL-1 lowered the abundance of Col2A1 mRNA in an NO-independent manner. Collectively, these data indicate that IL-1 suppresses collagen synthesis at two levels: a pretranslational level which is NO-independent, and a translational or post-translational level which is NO-mediated. These effects are presumably specific as L-NMA and SNAP had no effect on total protein synthesis or on the distribution of newly synthesized proteins between the cellular and extracellular compartments. Prolyl hydroxylase is an important enzyme in the post-translational processing of collagen, and its regulation and cofactor requirements suggest possible sensitivity to NO. Extracts of cells treated with IL-1 or SNAP had lower prolyl hydroxylase activity, and L-NMA was partially able to reverse the effects of IL-1. These data suggest that prolyl hydroxylase might indeed be a target for NO. Because under-hydroxylated collagen monomers fail to anneal into stable triple helices, they are degraded intracellularly. Inhibition of prolyl hydroxylase by NO might thus account for the suppressive effect of this radical on collagen synthesis.

AB - The addition of human recombinant interleukin-1β (IL-1β) to cultures of lapine articular chondrocytes provoked the synthesis of large amounts of NO and reduced the production of type-II collagen. N(G)-Monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, strongly suppressed the production of NO and partially relieved the inhibition of collagen synthesis in response to IL-1β. The NO donor S-nitrosoacetylpenicillamine (SNAP), on the other hand, inhibited collagen production. IL-1 lowered the abundance of Col2A1 mRNA in an NO-independent manner. Collectively, these data indicate that IL-1 suppresses collagen synthesis at two levels: a pretranslational level which is NO-independent, and a translational or post-translational level which is NO-mediated. These effects are presumably specific as L-NMA and SNAP had no effect on total protein synthesis or on the distribution of newly synthesized proteins between the cellular and extracellular compartments. Prolyl hydroxylase is an important enzyme in the post-translational processing of collagen, and its regulation and cofactor requirements suggest possible sensitivity to NO. Extracts of cells treated with IL-1 or SNAP had lower prolyl hydroxylase activity, and L-NMA was partially able to reverse the effects of IL-1. These data suggest that prolyl hydroxylase might indeed be a target for NO. Because under-hydroxylated collagen monomers fail to anneal into stable triple helices, they are degraded intracellularly. Inhibition of prolyl hydroxylase by NO might thus account for the suppressive effect of this radical on collagen synthesis.

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