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Cyanide-induced apoptosis involves oxidative-stress-activated NF-kappaB in cortical neurons.
Toxicol Appl Pharmacol. 2000 Apr 15; 164(2):196-205.TA

Abstract

The central nervous system is one of the main target organs in cyanide toxicity. Primary cultured cortical neurons were used to study the cellular mechanisms underlying cyanide-induced cytotoxicity. After exposure to KCN (100-300 microM) for 24 h, cortical neurons underwent apoptosis as characterized by positive TUNEL staining. Reactive oxygen species (ROS) play an important role in cyanide-induced neuronal apoptosis; immediately after cyanide (100-300 microM) treatment, ROS generation was observed and continued to be elevated for up to 3 h. NMDA receptor activation and subsequent Ca(2+) influx contribute in part to cyanide-induced ROS formation, since the selective NMDA receptor antagonist MK801 and intracellular Ca(2+) chelator BAPTA blocked ROS generation. Interestingly, caspases, recently reported to be involved in neuronal apoptosis, play a role in the late phase of ROS production after cyanide stimulation. Z-VAD, a nonspecific caspase inhibitor, blocked ROS generated 1 h after cyanide treatment, but it had no effect on ROS generated immediately after cyanide treatment. Nuclear factor kappaB (NF-kappaB), a redox-sensitive transcription factor, was activated dose dependently after cyanide treatment. Blockade of ROS generation by MK801, Z-VAD, and various antioxidants also blocked the activation of NF-kappaB. SN50, a synthetic peptide which inhibits the nuclear translocation of NF-kappaB, blocked cyanide-induced apoptotic cell death. These results indicate that NF-kappaB plays an important role in cyanide-induced apoptosis in cortical neurons, and the caspases may contribute in part to the activation of NF-kappaB after cyanide treatment by inducing the late phase of ROS generation.

Authors+Show Affiliations

Neurotoxicology Laboratory, Purdue University, West Lafayette, Indiana 47907-1333, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10764633

Citation

Shou, Y, et al. "Cyanide-induced Apoptosis Involves Oxidative-stress-activated NF-kappaB in Cortical Neurons." Toxicology and Applied Pharmacology, vol. 164, no. 2, 2000, pp. 196-205.
Shou Y, Gunasekar PG, Borowitz JL, et al. Cyanide-induced apoptosis involves oxidative-stress-activated NF-kappaB in cortical neurons. Toxicol Appl Pharmacol. 2000;164(2):196-205.
Shou, Y., Gunasekar, P. G., Borowitz, J. L., & Isom, G. E. (2000). Cyanide-induced apoptosis involves oxidative-stress-activated NF-kappaB in cortical neurons. Toxicology and Applied Pharmacology, 164(2), 196-205.
Shou Y, et al. Cyanide-induced Apoptosis Involves Oxidative-stress-activated NF-kappaB in Cortical Neurons. Toxicol Appl Pharmacol. 2000 Apr 15;164(2):196-205. PubMed PMID: 10764633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyanide-induced apoptosis involves oxidative-stress-activated NF-kappaB in cortical neurons. AU - Shou,Y, AU - Gunasekar,P G, AU - Borowitz,J L, AU - Isom,G E, PY - 2000/4/15/pubmed PY - 2000/6/8/medline PY - 2000/4/15/entrez SP - 196 EP - 205 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 164 IS - 2 N2 - The central nervous system is one of the main target organs in cyanide toxicity. Primary cultured cortical neurons were used to study the cellular mechanisms underlying cyanide-induced cytotoxicity. After exposure to KCN (100-300 microM) for 24 h, cortical neurons underwent apoptosis as characterized by positive TUNEL staining. Reactive oxygen species (ROS) play an important role in cyanide-induced neuronal apoptosis; immediately after cyanide (100-300 microM) treatment, ROS generation was observed and continued to be elevated for up to 3 h. NMDA receptor activation and subsequent Ca(2+) influx contribute in part to cyanide-induced ROS formation, since the selective NMDA receptor antagonist MK801 and intracellular Ca(2+) chelator BAPTA blocked ROS generation. Interestingly, caspases, recently reported to be involved in neuronal apoptosis, play a role in the late phase of ROS production after cyanide stimulation. Z-VAD, a nonspecific caspase inhibitor, blocked ROS generated 1 h after cyanide treatment, but it had no effect on ROS generated immediately after cyanide treatment. Nuclear factor kappaB (NF-kappaB), a redox-sensitive transcription factor, was activated dose dependently after cyanide treatment. Blockade of ROS generation by MK801, Z-VAD, and various antioxidants also blocked the activation of NF-kappaB. SN50, a synthetic peptide which inhibits the nuclear translocation of NF-kappaB, blocked cyanide-induced apoptotic cell death. These results indicate that NF-kappaB plays an important role in cyanide-induced apoptosis in cortical neurons, and the caspases may contribute in part to the activation of NF-kappaB after cyanide treatment by inducing the late phase of ROS generation. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/10764633/Cyanide_induced_apoptosis_involves_oxidative_stress_activated_NF_kappaB_in_cortical_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(00)98900-2 DB - PRIME DP - Unbound Medicine ER -