Apoptosis markers are molecular targets of sulfure mustard toxic action

Cover Page

Cite item

Full Text

Abstract

Cellular in vitro test systems, which allow to determine apoptosis activation at different concentrations of sulfur mustard, were proposed. The efficiency of these test systems was evaluated by the action of N-acetylcysteine. As indicators of toxic effect, were evaluated an integral cytotoxicity and activation of the following targets: poly (ADP-ribose) polymerase (PARP1), caspase-3, caspase-9, transcription factor p53 and other markers of apoptosis in human SH-SY5Y cells extracts after sulfur mustard and sulfur mustard with N-acetylcysteine exposure. We can distinguished the following main target of sulfur mustard toxic action on the cells: caspase-3, caspase-9, PARP1 and p53 transcription factor, which in this system was the primary target and was activated after 6 h toxicant exposure. The active forms of enzymes caspase-3, caspase-9 and PARP1 significantly accumulate in cells after 24 h toxicant exposure.

About the authors

N. Yu. Rogovskaya

Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency

Author for correspondence.
Email: noemail@neicon.ru
Russian Federation

V. N. Babakov

Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency

Email: noemail@neicon.ru
Russian Federation

References

  1. Подольская Е.П., Бабаков В.Н. Масс-спектрометрия с мягкими методами ионизации в токсикологическом анализе. Научное приборостроение. 2008; 18 (4): 5-12.
  2. Краснов И.А., Подольская Е.П., Гончаров Н.В. и др. Идентификация алкилированного аддукта сывороточного альбумина человека методами масс-спектрометрии. Научное приборостроение. 2008; 18 (4): 46-53.
  3. Nourani M.R., Mahmoodzadeh Hosseini H., Azimzadeh Jamalkandi S., Imani Fooladi A.A. Cellular and molecular mechanisms of acute exposure to sulfur mustard: a systematic review. J Recept Signal Transduct Res. 2016; 2:1-
  4. Debiak M., kehe k., Burkle A. Role of poly(ADP-ribose) polymerase in sulfur mustard toxicity. Toxicology. 2009; 263:20–5.
  5. Byrne M.P., Broomfield C.A., Stites W.E. Mustard gas crosslinking of proteins through preferential alkylation of cysteines. J Protein Chem. 1996; 15:131–6.
  6. Ghabili k., Agutter P.S., Ghanei M., et al. Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics. Critical Rev Toxicol. 2011; 41:384–403.
  7. Minsavage G.D., Dillman J.F. 3rd. Bifunctional alkylating agent-induced p53 and nonclassical nuclear factor kappaB responses and cell death are altered by caffeic acid phenethyl ester: a potential role for antioxidant/electrophilic responseelement signaling. J Pharmacol Exp Ther. 2007; 321:202-12.
  8. Rebholz B., kehe k., Ruzicka T., Rupec R.A. Role of NF-kappaB/RelA and MAPK pathways in keratinocytes in response to sulfur mustard. J Invest Dermatol. 2008; 128(7):1626-32.
  9. Dillman J.F. 3rd, McGary K.L., Schlager J.J. An inhibitor of p38 MAP kinasedownregulates cytokine release induced by sulfur mustard exposure in humanepidermal keratinocytes. Toxicol In Vitro. 2004; 18(5):593-9.
  10. Schmidt B.Z., Lehmann M., Gutbier S., Nembo E., Noel S., Smirnova L.et al. In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities. Arch Toxicol. 2016: 1-doi: 10.1007/s00204-016-1805-9
  11. Szymanski P., Markowicz M., MikiciukOlasik E. Adaptation of high-throughput screening in drug discovery-toxicological screening tests. Int J Mol Sci.2012; 13(1):427-
  12. Ozsvari B., Puskas L. G., Nagy L. I., kanizsai I., Gyuris M., Madácsi R., et al. A cell-microelectronic sensing technique for the screening of cytoprotective compounds. International journal of molecular medicine. 2010; 25(4): 525-30.
  13. Jayaraman A., Pike C.J. Progesterone attenuates oestrogen neuroprotection via downregulation of oestrogen receptor expression in cultured neurones. J. Neuroendocrinol. 2009; 21(1):77-
  14. Tarze A., Deniaud A., Le Bras M., Maillier E., Molle D., Larochette N., et al. GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization. Oncogene. 2007; 26(18): 2606–20.
  15. Malaviya R., Sunil V.R., Cervelli J., Anderson D.R., Holmes W.W., Conti M.L., et al. Inflammatory effects of inhaled sulfur mustard in rat lung. Toxicol Appl Pharmacol. 2010; 248 (2):89–99.
  16. Ruff A.L., Dillman J.F. 3rd Signaling molecules in sulfur mustard-induced cutaneous injury. ePlasty. 2008; 8: 8-22.
  17. Толкач П.Г., Башарин В.А., Колобов А.А., Роговская Н.Ю., Бабаков В.Н. Влияние пептида КК1 на содержание маркеров апоптоза в головном мозге крыс после острой тяжелой интоксикации оксидом углерода. Токсикологический вестник. 2016; (3):10-4.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Rogovskaya N.Y., Babakov V.N.


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 81728 от 11 декабря 2013.