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Thiol antioxidant reversal of pyrrolidine dithiocarbamate-induced reciprocal regulation of AP-1 and NF-kappaB.
Biol Chem. 2003 Jan; 384(1):143-50.BC

Abstract

Pyrrolidine dithiocarbamate (PDTC) has been shown to have unique reciprocal activities in activating AP-1 and inhibiting NF-kappaB, two oxidative stress-sensitive transcription factors. The opposing effects of PDTC on these two transcription factors have been attributed to its thiol antioxidant properties. In the present study, PDTC activation of AP-1, like its inhibition of NF-kappaB, in bovine cerebral endothelial cells (BCECs) was zinc-dependent, consistent with the contention that PDTC acts as a zinc ionophore and the apparent reciprocal actions of PDTC are mediated by zinc. Unlike PDTC, other thiols and non-thiol antioxidants did not activate AP-1 on their own. Thiol, but not non-thiol, antioxidants reversed PDTC actions on AP-1 and NF-kappaB. PDTC reduced the intracellular glutathione content, and depletion of the cellular glutathione store by buthionine sulfoximine (BSO) further augmented PDTC actions on AP-1 and NF-kappaB. N-acetylcysteine (NAC), a thiol antioxidant, reversed PDTC actions even after irreversible depletion of the cellular glutathione store by BSO. These findings together suggest that thiol antioxidant reversal of PDTC actions on AP-1 and NF-kappaB is independent of their established roles in scavenging oxygen free radicals or repleting the cellular glutathione content. The results in the present and earlier studies suggest that thiol antioxidants are likely to act as metal chelators that buffer zinc mediation of the reciprocal actions of PDTC on AP-1 and NF-kappaB.

Authors+Show Affiliations

Brain Korea 21 Project for Medical Sciences, Brain Research Institute and Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea.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

Language

eng

PubMed ID

12674508

Citation

Kim, Chul Hoon, et al. "Thiol Antioxidant Reversal of Pyrrolidine Dithiocarbamate-induced Reciprocal Regulation of AP-1 and NF-kappaB." Biological Chemistry, vol. 384, no. 1, 2003, pp. 143-50.
Kim CH, Kim JH, Lee J, et al. Thiol antioxidant reversal of pyrrolidine dithiocarbamate-induced reciprocal regulation of AP-1 and NF-kappaB. Biol Chem. 2003;384(1):143-50.
Kim, C. H., Kim, J. H., Lee, J., Hsu, C. Y., & Ahn, Y. S. (2003). Thiol antioxidant reversal of pyrrolidine dithiocarbamate-induced reciprocal regulation of AP-1 and NF-kappaB. Biological Chemistry, 384(1), 143-50.
Kim CH, et al. Thiol Antioxidant Reversal of Pyrrolidine Dithiocarbamate-induced Reciprocal Regulation of AP-1 and NF-kappaB. Biol Chem. 2003;384(1):143-50. PubMed PMID: 12674508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thiol antioxidant reversal of pyrrolidine dithiocarbamate-induced reciprocal regulation of AP-1 and NF-kappaB. AU - Kim,Chul Hoon, AU - Kim,Joo Hee, AU - Lee,Jinu, AU - Hsu,Chung Y, AU - Ahn,Young Soo, PY - 2003/4/4/pubmed PY - 2003/10/15/medline PY - 2003/4/4/entrez SP - 143 EP - 50 JF - Biological chemistry JO - Biol Chem VL - 384 IS - 1 N2 - Pyrrolidine dithiocarbamate (PDTC) has been shown to have unique reciprocal activities in activating AP-1 and inhibiting NF-kappaB, two oxidative stress-sensitive transcription factors. The opposing effects of PDTC on these two transcription factors have been attributed to its thiol antioxidant properties. In the present study, PDTC activation of AP-1, like its inhibition of NF-kappaB, in bovine cerebral endothelial cells (BCECs) was zinc-dependent, consistent with the contention that PDTC acts as a zinc ionophore and the apparent reciprocal actions of PDTC are mediated by zinc. Unlike PDTC, other thiols and non-thiol antioxidants did not activate AP-1 on their own. Thiol, but not non-thiol, antioxidants reversed PDTC actions on AP-1 and NF-kappaB. PDTC reduced the intracellular glutathione content, and depletion of the cellular glutathione store by buthionine sulfoximine (BSO) further augmented PDTC actions on AP-1 and NF-kappaB. N-acetylcysteine (NAC), a thiol antioxidant, reversed PDTC actions even after irreversible depletion of the cellular glutathione store by BSO. These findings together suggest that thiol antioxidant reversal of PDTC actions on AP-1 and NF-kappaB is independent of their established roles in scavenging oxygen free radicals or repleting the cellular glutathione content. The results in the present and earlier studies suggest that thiol antioxidants are likely to act as metal chelators that buffer zinc mediation of the reciprocal actions of PDTC on AP-1 and NF-kappaB. SN - 1431-6730 UR - https://www.unboundmedicine.com/medline/citation/12674508/Thiol_antioxidant_reversal_of_pyrrolidine_dithiocarbamate_induced_reciprocal_regulation_of_AP_1_and_NF_kappaB_ L2 - https://www.degruyter.com/document/doi/10.1515/BC.2003.015 DB - PRIME DP - Unbound Medicine ER -