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Constitutive nuclear NF kappa B/rel DNA-binding activity of rat thymocytes is increased by stimuli that promote apoptosis, but not inhibited by pyrrolidine dithiocarbamate.
Biochem J. 1995 Dec 15; 312 (Pt 3):833-8.BJ

Abstract

Rat thymocytes spontaneously undergo apoptotic death in cell culture, and are also sensitive to the induction of apoptosis by various stimuli. We show that unstimulated thymocytes constitutively express a p50-containing nuclear factor kappa B (NF kappa B)/rel DNA-binding activity in their nuclei. When the cells were fractionated by density-gradient centrifugation this activity was found to be most pronounced in immature CD4+8+ thymocytes, the cell population that undergoes selection by apoptosis in vivo and that is most sensitive to external inducers of apoptosis in vitro. The intensity of the NF kappa B/rel protein-DNA complex was significantly enhanced 30 min after exposing thymocytes to methylprednisolone or etoposide, two agents well known to induce apoptosis in these cells. Expression of this DNA-binding activity therefore correlates with the subsequent occurrence of apoptosis. By analogy to other systems, it has been suggested that antioxidants such as pyrrolidine dithiocarbamate (PDTC) inhibit thymocyte apoptosis by preventing the activation of an NF kappa B/rel transcription factor. However, we have found that etoposide induces a very similar enhancement of the NF kappa B/rel DNA-binding activity in the presence or absence of PDTC, despite a pronounced inhibition of apoptotic DNA fragmentation in the former situation. Dithiocarbamates therefore do not exert their anti-apoptotic activity in thymocytes by inhibiting the activation of this transcription factor.

Authors+Show Affiliations

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.No 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

8554528

Citation

Slater, A F., et al. "Constitutive Nuclear NF Kappa B/rel DNA-binding Activity of Rat Thymocytes Is Increased By Stimuli That Promote Apoptosis, but Not Inhibited By Pyrrolidine Dithiocarbamate." The Biochemical Journal, vol. 312 (Pt 3), 1995, pp. 833-8.
Slater AF, Kimland M, Jiang SA, et al. Constitutive nuclear NF kappa B/rel DNA-binding activity of rat thymocytes is increased by stimuli that promote apoptosis, but not inhibited by pyrrolidine dithiocarbamate. Biochem J. 1995;312 (Pt 3):833-8.
Slater, A. F., Kimland, M., Jiang, S. A., & Orrenius, S. (1995). Constitutive nuclear NF kappa B/rel DNA-binding activity of rat thymocytes is increased by stimuli that promote apoptosis, but not inhibited by pyrrolidine dithiocarbamate. The Biochemical Journal, 312 (Pt 3), 833-8.
Slater AF, et al. Constitutive Nuclear NF Kappa B/rel DNA-binding Activity of Rat Thymocytes Is Increased By Stimuli That Promote Apoptosis, but Not Inhibited By Pyrrolidine Dithiocarbamate. Biochem J. 1995 Dec 15;312 (Pt 3):833-8. PubMed PMID: 8554528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Constitutive nuclear NF kappa B/rel DNA-binding activity of rat thymocytes is increased by stimuli that promote apoptosis, but not inhibited by pyrrolidine dithiocarbamate. AU - Slater,A F, AU - Kimland,M, AU - Jiang,S A, AU - Orrenius,S, PY - 1995/12/15/pubmed PY - 1995/12/15/medline PY - 1995/12/15/entrez SP - 833 EP - 8 JF - The Biochemical journal JO - Biochem J VL - 312 (Pt 3) N2 - Rat thymocytes spontaneously undergo apoptotic death in cell culture, and are also sensitive to the induction of apoptosis by various stimuli. We show that unstimulated thymocytes constitutively express a p50-containing nuclear factor kappa B (NF kappa B)/rel DNA-binding activity in their nuclei. When the cells were fractionated by density-gradient centrifugation this activity was found to be most pronounced in immature CD4+8+ thymocytes, the cell population that undergoes selection by apoptosis in vivo and that is most sensitive to external inducers of apoptosis in vitro. The intensity of the NF kappa B/rel protein-DNA complex was significantly enhanced 30 min after exposing thymocytes to methylprednisolone or etoposide, two agents well known to induce apoptosis in these cells. Expression of this DNA-binding activity therefore correlates with the subsequent occurrence of apoptosis. By analogy to other systems, it has been suggested that antioxidants such as pyrrolidine dithiocarbamate (PDTC) inhibit thymocyte apoptosis by preventing the activation of an NF kappa B/rel transcription factor. However, we have found that etoposide induces a very similar enhancement of the NF kappa B/rel DNA-binding activity in the presence or absence of PDTC, despite a pronounced inhibition of apoptotic DNA fragmentation in the former situation. Dithiocarbamates therefore do not exert their anti-apoptotic activity in thymocytes by inhibiting the activation of this transcription factor. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/8554528/Constitutive_nuclear_NF_kappa_B/rel_DNA_binding_activity_of_rat_thymocytes_is_increased_by_stimuli_that_promote_apoptosis_but_not_inhibited_by_pyrrolidine_dithiocarbamate_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/bj3120833 DB - PRIME DP - Unbound Medicine ER -