The oxygen radical scavenger pyrrolidine dithiocarbamate enhances interleukin-1β-induced cyclooxygenase-2 expression in cerebral microvascular smooth muscle cells

Xiang Fang, Ping Chen, Steven A. Moore

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Oxidative stress and inducible cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) formation have been proposed to play an important role in cytokine-induced vascular pathology. To explore the relationship between oxidative stress and COX-2 induction, cultured murine cerebral microvascular smooth muscle cells (SMCs) were stimulated with interleukin-1β (IL-1β) in the presence or absence of an oxygen radical scavenger, pyrrolidine dithiocarbamate (PDTC). IL-1β increased COX-2 protein expression in a dose- and time-dependent manner, an increase that was further enhanced by PDTC in a dose-dependent manner. PDTC did not, however, affect the expression of COX-1 protein. In the presence of 100 μM PDTC, PGE2 production induced by IL-1β (5 ng/ml) was increased by threefold as compared with IL-1β alone. Although PDTC enhanced COX-2 protein expression, it did not increase IL-1β-induced expression of COX-2 mRNA, indicating that the regulatory effect occurred at the posttranscriptional level. The time course of COX-2 protein degradation indicated that PDTC also did not alter the stability of the COX-2 protein induced by IL-1β. These results suggest that endogenous oxygen radicals may blunt COX-2 induced by IL-1β through an effect on translation.

Original languageEnglish (US)
Pages (from-to)405-413
Number of pages9
JournalMicrovascular Research
Volume64
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Interleukin-1
Smooth Muscle Myocytes
Muscle
Reactive Oxygen Species
Cells
Oxidative stress
Proteins
Oxidative Stress
pyrrolidine dithiocarbamic acid
Interleukin-5
Pathology
Dinoprostone
Proteolysis
Prostaglandins
Blood Vessels
Cytokines
Degradation
Messenger RNA

Keywords

  • Cyclooxygenase 2
  • Interleukin-1β
  • Oxidative stress
  • Smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "The oxygen radical scavenger pyrrolidine dithiocarbamate enhances interleukin-1β-induced cyclooxygenase-2 expression in cerebral microvascular smooth muscle cells",
abstract = "Oxidative stress and inducible cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) formation have been proposed to play an important role in cytokine-induced vascular pathology. To explore the relationship between oxidative stress and COX-2 induction, cultured murine cerebral microvascular smooth muscle cells (SMCs) were stimulated with interleukin-1β (IL-1β) in the presence or absence of an oxygen radical scavenger, pyrrolidine dithiocarbamate (PDTC). IL-1β increased COX-2 protein expression in a dose- and time-dependent manner, an increase that was further enhanced by PDTC in a dose-dependent manner. PDTC did not, however, affect the expression of COX-1 protein. In the presence of 100 μM PDTC, PGE2 production induced by IL-1β (5 ng/ml) was increased by threefold as compared with IL-1β alone. Although PDTC enhanced COX-2 protein expression, it did not increase IL-1β-induced expression of COX-2 mRNA, indicating that the regulatory effect occurred at the posttranscriptional level. The time course of COX-2 protein degradation indicated that PDTC also did not alter the stability of the COX-2 protein induced by IL-1β. These results suggest that endogenous oxygen radicals may blunt COX-2 induced by IL-1β through an effect on translation.",
keywords = "Cyclooxygenase 2, Interleukin-1β, Oxidative stress, Smooth muscle cells",
author = "Xiang Fang and Ping Chen and Moore, {Steven A.}",
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TY - JOUR

T1 - The oxygen radical scavenger pyrrolidine dithiocarbamate enhances interleukin-1β-induced cyclooxygenase-2 expression in cerebral microvascular smooth muscle cells

AU - Fang, Xiang

AU - Chen, Ping

AU - Moore, Steven A.

PY - 2002

Y1 - 2002

N2 - Oxidative stress and inducible cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) formation have been proposed to play an important role in cytokine-induced vascular pathology. To explore the relationship between oxidative stress and COX-2 induction, cultured murine cerebral microvascular smooth muscle cells (SMCs) were stimulated with interleukin-1β (IL-1β) in the presence or absence of an oxygen radical scavenger, pyrrolidine dithiocarbamate (PDTC). IL-1β increased COX-2 protein expression in a dose- and time-dependent manner, an increase that was further enhanced by PDTC in a dose-dependent manner. PDTC did not, however, affect the expression of COX-1 protein. In the presence of 100 μM PDTC, PGE2 production induced by IL-1β (5 ng/ml) was increased by threefold as compared with IL-1β alone. Although PDTC enhanced COX-2 protein expression, it did not increase IL-1β-induced expression of COX-2 mRNA, indicating that the regulatory effect occurred at the posttranscriptional level. The time course of COX-2 protein degradation indicated that PDTC also did not alter the stability of the COX-2 protein induced by IL-1β. These results suggest that endogenous oxygen radicals may blunt COX-2 induced by IL-1β through an effect on translation.

AB - Oxidative stress and inducible cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) formation have been proposed to play an important role in cytokine-induced vascular pathology. To explore the relationship between oxidative stress and COX-2 induction, cultured murine cerebral microvascular smooth muscle cells (SMCs) were stimulated with interleukin-1β (IL-1β) in the presence or absence of an oxygen radical scavenger, pyrrolidine dithiocarbamate (PDTC). IL-1β increased COX-2 protein expression in a dose- and time-dependent manner, an increase that was further enhanced by PDTC in a dose-dependent manner. PDTC did not, however, affect the expression of COX-1 protein. In the presence of 100 μM PDTC, PGE2 production induced by IL-1β (5 ng/ml) was increased by threefold as compared with IL-1β alone. Although PDTC enhanced COX-2 protein expression, it did not increase IL-1β-induced expression of COX-2 mRNA, indicating that the regulatory effect occurred at the posttranscriptional level. The time course of COX-2 protein degradation indicated that PDTC also did not alter the stability of the COX-2 protein induced by IL-1β. These results suggest that endogenous oxygen radicals may blunt COX-2 induced by IL-1β through an effect on translation.

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KW - Interleukin-1β

KW - Oxidative stress

KW - Smooth muscle cells

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