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Selective activation of endothelial cells by the antioxidant pyrrolidine dithiocarbamate: involvement of C-jun N-terminal kinase and AP-1 activation.
Endothelium. 2000; 7(2):121-33.E

Abstract

The antioxidant agent pyrrolidine dithiocarbamate (PDTC) has been shown to protect endothelial cells (EC) from pro-inflammatory-induced and pro-oxidant-induced NF-kappaB activation. It also perturbs EC by altering activator protein-1 (AP-1) status and inducing ICAM-1. Experiments were performed to investigate the upstream mechanism by which PDTC produces these effects. We have demonstrated that PDTC not only induced AP-1 binding and ICAM-1 expression by itself, but it also augmented AP-1 activation and ICAM-1 induction in low-dose IL-1alpha treated cells. To dissect the mechanism of these effects, we measured c-Jun and c-Fos expression, and the activity of c-Jun NH2-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) in human umbilical vein endothelial cells (HUVEC). We detected an increase in JNK activity in PDTC-treated HUVEC. Following cotransfection with JNK[K-M], a kinase-deficient JNK1, the PDTC-increased AP-1-driven-luciferase activity was attenuated. Utilizing a specific trans-reporting system we confirmed c-Jun activation by upstream signaling mechanisms. The results show that c-Jun activity was increased 9-fold after PDTC treatment. In addition, PDTC promoted more transient activation in ERK-c-fos. In contrast, PDTC produced sustained JNK-c-Jun activation, which translated into long-lasting ICAM-1 production. These results suggest that an antioxidant may contribute to chronic vascular endothelial activation.

Authors+Show Affiliations

Division of Biomedical Sciences, University of California, Riverside 92521, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10865940

Citation

Liao, H L., et al. "Selective Activation of Endothelial Cells By the Antioxidant Pyrrolidine Dithiocarbamate: Involvement of C-jun N-terminal Kinase and AP-1 Activation." Endothelium : Journal of Endothelial Cell Research, vol. 7, no. 2, 2000, pp. 121-33.
Liao HL, Zhu Y, Wang N, et al. Selective activation of endothelial cells by the antioxidant pyrrolidine dithiocarbamate: involvement of C-jun N-terminal kinase and AP-1 activation. Endothelium. 2000;7(2):121-33.
Liao, H. L., Zhu, Y., Wang, N., Verna, L., & Stemerman, M. B. (2000). Selective activation of endothelial cells by the antioxidant pyrrolidine dithiocarbamate: involvement of C-jun N-terminal kinase and AP-1 activation. Endothelium : Journal of Endothelial Cell Research, 7(2), 121-33.
Liao HL, et al. Selective Activation of Endothelial Cells By the Antioxidant Pyrrolidine Dithiocarbamate: Involvement of C-jun N-terminal Kinase and AP-1 Activation. Endothelium. 2000;7(2):121-33. PubMed PMID: 10865940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective activation of endothelial cells by the antioxidant pyrrolidine dithiocarbamate: involvement of C-jun N-terminal kinase and AP-1 activation. AU - Liao,H L, AU - Zhu,Y, AU - Wang,N, AU - Verna,L, AU - Stemerman,M B, PY - 2000/6/24/pubmed PY - 2000/10/7/medline PY - 2000/6/24/entrez SP - 121 EP - 33 JF - Endothelium : journal of endothelial cell research JO - Endothelium VL - 7 IS - 2 N2 - The antioxidant agent pyrrolidine dithiocarbamate (PDTC) has been shown to protect endothelial cells (EC) from pro-inflammatory-induced and pro-oxidant-induced NF-kappaB activation. It also perturbs EC by altering activator protein-1 (AP-1) status and inducing ICAM-1. Experiments were performed to investigate the upstream mechanism by which PDTC produces these effects. We have demonstrated that PDTC not only induced AP-1 binding and ICAM-1 expression by itself, but it also augmented AP-1 activation and ICAM-1 induction in low-dose IL-1alpha treated cells. To dissect the mechanism of these effects, we measured c-Jun and c-Fos expression, and the activity of c-Jun NH2-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) in human umbilical vein endothelial cells (HUVEC). We detected an increase in JNK activity in PDTC-treated HUVEC. Following cotransfection with JNK[K-M], a kinase-deficient JNK1, the PDTC-increased AP-1-driven-luciferase activity was attenuated. Utilizing a specific trans-reporting system we confirmed c-Jun activation by upstream signaling mechanisms. The results show that c-Jun activity was increased 9-fold after PDTC treatment. In addition, PDTC promoted more transient activation in ERK-c-fos. In contrast, PDTC produced sustained JNK-c-Jun activation, which translated into long-lasting ICAM-1 production. These results suggest that an antioxidant may contribute to chronic vascular endothelial activation. SN - 1062-3329 UR - https://www.unboundmedicine.com/medline/citation/10865940/Selective_activation_of_endothelial_cells_by_the_antioxidant_pyrrolidine_dithiocarbamate:_involvement_of_C_jun_N_terminal_kinase_and_AP_1_activation_ L2 - https://medlineplus.gov/antioxidants.html DB - PRIME DP - Unbound Medicine ER -