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NRF2 and HMOX1 Gene Expression against the Background of Systemic Oxidative Stress in Patients with Acute Psychosis

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Abstract

The aim of this study was to evaluate NRF2 and HMOX1 gene expression against the background of systemic oxidative stress in patients with acute psychosis. The study included 40 patients with newly developed paranoid schizophrenia, 22 subjects with new-onset acute psychosis associated with excessive alcohol consumption, and 25 healthy volunteers. The signs of systemic oxidative stress were assessed by 8-dihydro-2'-deoxyguanosine (8-oxodG) contents in peripheral blood lymphocytes (PBL) and in cell-free (cf) DNA samples obtained from plasma specimens of the patients and healthy controls. The patients of both groups demonstrated a significant (a hundredfold) increase in 8-oxodG content in cfDNA samples and a marked (5- to 8-fold) elevation of 8-oxodG concentration in PBL. Against the background of systemic oxidative stress, there was a statistically significant increase in NRF2 protein expression as well as marked elevation of NRF2 and Hmox1 gene transcriptional activity in PBL obtained from alcoholic patients. In contrast, the subjects with newly developed paranoid schizophrenia demonstrated decrease in expression of NRF2, the master regulator of anti-oxidant defenses, as well as reduction of NRF-2 and Hmox1 gene transcriptional activity compared to both healthy controls and alcoholic patients. In conclusion, against the background of systemic oxidative stress associated acute psychosis development, PBL of patients with paranoid schizophrenia was characterized by reduced NRF2 gene transcriptional activity and decreased NRF2 protein expression.

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Funding

This work was financially supported by the Russian Foundation for Basic Research, project no. 17-29-06017ofi_m, and within the framework of the state assignment of the Russian Ministry of Education and Science.

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Correspondence to G. V. Shmarina.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in the study involving people comply with the ethical standards of the institutional and/or national research ethics committee and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards.

Informed consent was obtained from each of the participants in the study.

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Shmarina, G.V., Orlova, M.D., Ershova, E.S. et al. NRF2 and HMOX1 Gene Expression against the Background of Systemic Oxidative Stress in Patients with Acute Psychosis. Russ J Genet 56, 96–102 (2020). https://doi.org/10.1134/S102279542001010X

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Keywords:

  • oxidative stress
  • NRF-2
  • Hmox1
  • KEAP1
  • cell-free DNA
  • 8-dihydro-2'-deoxyguanosine
  • schizophrenia
  • alcoholism