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Pyrrolidine dithiocarbamate inhibits TNF-alpha-dependent activation of NF-kappaB by increasing intracellular copper level in human aortic smooth muscle cells.
Biochem Biophys Res Commun. 2000 Sep 16; 276(1):88-92.BB

Abstract

Pyrrolidine dithiocarbamate (PDTC) is a metal-chelating compound that acts as antioxidant or pro-oxidant and is widely used to study redox regulation of cell function. In the present study, we investigated effects of PDTC and another antioxidant, N-acetyl-l-cysteine (NAC), on TNF-alpha-dependent activation of NF-kappaB in human aortic smooth muscle cells (HASMC). Treatment of the cells with TNF-alpha induced the activation of p65/p50 heterodimer NF-kappaB and increased the mRNA levels of monocyte chemoattractant protein (MCP)-1. Pretreatment with PDTC markedly suppressed the NF-kappaB activation and expression of MCP-1 by inhibiting IkappaB-alpha degradation. In contrast, NAC had no effect. PDTC concomitantly increased the intracellular levels of copper, and bathocuproinedisulfonic acid, a non-cell-permeable chelator of Cu(1+), inhibited the PDTC-induced increase in intracellular copper level and reversed the PDTC effects on IkappaB-alpha, NF-kappaB, and MCP-1. These results indicate that TNF-alpha-dependent expression of MCP-1 in HASMC is tightly regulated by NF-kappaB and that intracellular copper level is crucial for the TNF-alpha-dependent activation of NF-kappaB in HASMC.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya, 464-8601, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11006087

Citation

Iseki, A, et al. "Pyrrolidine Dithiocarbamate Inhibits TNF-alpha-dependent Activation of NF-kappaB By Increasing Intracellular Copper Level in Human Aortic Smooth Muscle Cells." Biochemical and Biophysical Research Communications, vol. 276, no. 1, 2000, pp. 88-92.
Iseki A, Kambe F, Okumura K, et al. Pyrrolidine dithiocarbamate inhibits TNF-alpha-dependent activation of NF-kappaB by increasing intracellular copper level in human aortic smooth muscle cells. Biochem Biophys Res Commun. 2000;276(1):88-92.
Iseki, A., Kambe, F., Okumura, K., Niwata, S., Yamamoto, R., Hayakawa, T., & Seo, H. (2000). Pyrrolidine dithiocarbamate inhibits TNF-alpha-dependent activation of NF-kappaB by increasing intracellular copper level in human aortic smooth muscle cells. Biochemical and Biophysical Research Communications, 276(1), 88-92.
Iseki A, et al. Pyrrolidine Dithiocarbamate Inhibits TNF-alpha-dependent Activation of NF-kappaB By Increasing Intracellular Copper Level in Human Aortic Smooth Muscle Cells. Biochem Biophys Res Commun. 2000 Sep 16;276(1):88-92. PubMed PMID: 11006087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pyrrolidine dithiocarbamate inhibits TNF-alpha-dependent activation of NF-kappaB by increasing intracellular copper level in human aortic smooth muscle cells. AU - Iseki,A, AU - Kambe,F, AU - Okumura,K, AU - Niwata,S, AU - Yamamoto,R, AU - Hayakawa,T, AU - Seo,H, PY - 2000/9/28/pubmed PY - 2001/2/28/medline PY - 2000/9/28/entrez SP - 88 EP - 92 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 276 IS - 1 N2 - Pyrrolidine dithiocarbamate (PDTC) is a metal-chelating compound that acts as antioxidant or pro-oxidant and is widely used to study redox regulation of cell function. In the present study, we investigated effects of PDTC and another antioxidant, N-acetyl-l-cysteine (NAC), on TNF-alpha-dependent activation of NF-kappaB in human aortic smooth muscle cells (HASMC). Treatment of the cells with TNF-alpha induced the activation of p65/p50 heterodimer NF-kappaB and increased the mRNA levels of monocyte chemoattractant protein (MCP)-1. Pretreatment with PDTC markedly suppressed the NF-kappaB activation and expression of MCP-1 by inhibiting IkappaB-alpha degradation. In contrast, NAC had no effect. PDTC concomitantly increased the intracellular levels of copper, and bathocuproinedisulfonic acid, a non-cell-permeable chelator of Cu(1+), inhibited the PDTC-induced increase in intracellular copper level and reversed the PDTC effects on IkappaB-alpha, NF-kappaB, and MCP-1. These results indicate that TNF-alpha-dependent expression of MCP-1 in HASMC is tightly regulated by NF-kappaB and that intracellular copper level is crucial for the TNF-alpha-dependent activation of NF-kappaB in HASMC. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/11006087/Pyrrolidine_dithiocarbamate_inhibits_TNF_alpha_dependent_activation_of_NF_kappaB_by_increasing_intracellular_copper_level_in_human_aortic_smooth_muscle_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(00)93452-1 DB - PRIME DP - Unbound Medicine ER -