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Anthrax Protective Antigen 63 (PA63): Toxic Effects in Neural Cultures and Role in Gulf War Illness (GWI).
Neurosci Insights. 2020; 15:2633105520931966.NI

Abstract

Protective antigen (PA) 63 (PA63) is a protein derived from the PA83 component contained in the anthrax vaccine. The anthrax vaccine ("Biothrax") was administered together with other vaccines to Gulf War veterans, about 35% of whom later developed a multisymptom disease (Gulf War Illness [GWI]), with prominent neurological/cognitive/mood symptoms, among others. The disease has been traditionally attributed to exposures to toxic chemicals during the war but other factors could be involved, including vaccines received. Of these, the anthrax vaccine is the most toxic. Here, we assessed directly the PA63 toxin's harmful effects on cultured neuroblastoma 2A (N2A) cells with respect to cell spreading, process formation, apoptosis, and integrity of cell membrane, cytoskeleton, and mitochondria. We found that, when added in N2A cultures, PA63 toxin led to decreased cell spreading and cell aggregation, leading to apoptosis. The mechanisms of PA63-induced cell damage included compromised cell membrane permeability indicated by enhanced access of propidium iodide in cells. In addition, signaling pathways leading to organization of N2A cytoskeleton were negatively affected, as both actin and microtubular networks were compromised. Finally, the mitochondrial membrane potential was impaired in specific assays. Altogether, these alterations led to apoptosis as a collective toxic effect of PA63 which was substantially reduced by the concomitant addition of specific antibodies against PA63.

Authors+Show Affiliations

Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA. Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, MN, USA.Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA.Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA. Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, MN, USA.Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA. Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, MN, USA. Department of Psychiatry, Medical School, University of Minnesota, Minneapolis, MN, USA.Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA. Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, MN, USA. Department of Psychology, University of Minnesota, Minneapolis, MN, USA.Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA. Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, MN, USA. Department of Psychiatry, Medical School, University of Minnesota, Minneapolis, MN, USA. Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32656531

Citation

Tsilibary, Effie-Photini C., et al. "Anthrax Protective Antigen 63 (PA63): Toxic Effects in Neural Cultures and Role in Gulf War Illness (GWI)." Neuroscience Insights, vol. 15, 2020, p. 2633105520931966.
Tsilibary EC, Souto EP, Kratzke M, et al. Anthrax Protective Antigen 63 (PA63): Toxic Effects in Neural Cultures and Role in Gulf War Illness (GWI). Neurosci Insights. 2020;15:2633105520931966.
Tsilibary, E. C., Souto, E. P., Kratzke, M., James, L. M., Engdahl, B. E., & Georgopoulos, A. P. (2020). Anthrax Protective Antigen 63 (PA63): Toxic Effects in Neural Cultures and Role in Gulf War Illness (GWI). Neuroscience Insights, 15, 2633105520931966. https://doi.org/10.1177/2633105520931966
Tsilibary EC, et al. Anthrax Protective Antigen 63 (PA63): Toxic Effects in Neural Cultures and Role in Gulf War Illness (GWI). Neurosci Insights. 2020;15:2633105520931966. PubMed PMID: 32656531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anthrax Protective Antigen 63 (PA63): Toxic Effects in Neural Cultures and Role in Gulf War Illness (GWI). AU - Tsilibary,Effie-Photini C, AU - Souto,Eric P, AU - Kratzke,Marian, AU - James,Lisa M, AU - Engdahl,Brian E, AU - Georgopoulos,Apostolos P, Y1 - 2020/06/30/ PY - 2020/03/19/received PY - 2020/05/14/accepted PY - 2020/7/14/entrez PY - 2020/7/14/pubmed PY - 2020/7/14/medline KW - Gulf War Illness KW - N2A cultures KW - anthrax PA63 KW - apoptosis KW - cytoskeleton KW - membrane permeability KW - mitochondrial membrane potential SP - 2633105520931966 EP - 2633105520931966 JF - Neuroscience insights JO - Neurosci Insights VL - 15 N2 - Protective antigen (PA) 63 (PA63) is a protein derived from the PA83 component contained in the anthrax vaccine. The anthrax vaccine ("Biothrax") was administered together with other vaccines to Gulf War veterans, about 35% of whom later developed a multisymptom disease (Gulf War Illness [GWI]), with prominent neurological/cognitive/mood symptoms, among others. The disease has been traditionally attributed to exposures to toxic chemicals during the war but other factors could be involved, including vaccines received. Of these, the anthrax vaccine is the most toxic. Here, we assessed directly the PA63 toxin's harmful effects on cultured neuroblastoma 2A (N2A) cells with respect to cell spreading, process formation, apoptosis, and integrity of cell membrane, cytoskeleton, and mitochondria. We found that, when added in N2A cultures, PA63 toxin led to decreased cell spreading and cell aggregation, leading to apoptosis. The mechanisms of PA63-induced cell damage included compromised cell membrane permeability indicated by enhanced access of propidium iodide in cells. In addition, signaling pathways leading to organization of N2A cytoskeleton were negatively affected, as both actin and microtubular networks were compromised. Finally, the mitochondrial membrane potential was impaired in specific assays. Altogether, these alterations led to apoptosis as a collective toxic effect of PA63 which was substantially reduced by the concomitant addition of specific antibodies against PA63. SN - 2633-1055 UR - https://www.unboundmedicine.com/medline/citation/32656531/Anthrax_Protective_Antigen_63_(PA63):_Toxic_Effects_in_Neural_Cultures_and_Role_in_Gulf_War_Illness_(GWI) L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32656531/ DB - PRIME DP - Unbound Medicine ER -
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