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RAS BiologyМолекулярная биология Molecular Biology

  • ISSN (Print) 0026-8984
  • ISSN (Online) 3034-5553

Regulation of Complement C3 Gene in the Human Hepatoma Cells HepG2 under Oxidative Stress

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PII
S30345553S0026898425040094-1
DOI
10.7868/S3034555325040094
Publication type
Article
Status
Published
Authors
A. V. Babina
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
V. S. Shavva
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
A. V. Lisunov
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
G. N. Oleinikova
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
E. E. Larionova
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
A. A. Dmitrieva
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
E. V. Nekrasova
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
S. V. Orlov
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
Volume/ Edition
Volume 59 / Issue number 4
Pages
629-645
Abstract
Accumulation of reactive oxygen and nitrogen species in cells during oxidative stress leads to oxidative damage to various cellular components, including DNA, proteins, and lipids, and, as a consequence, to the development of a number of severe diseases, such as atherosclerosis. Protein C3 is a central component of the complement cascade and a key player in the immune system. Proinflammatory activity of C3 can also contribute to the development of metabolic syndrome. Although hepatocytes are the main source of C3 in blood, regulation of C3 gene expression in hepatocytes under oxidative stress remains unexplored. Here we observe the suppression of C3 transcription and secretion during hydrogen peroxide-induced oxidative stress in human hepatoma cells HepG2. Transcription factor FOXO1 promoted C3 expression, and C3 repression by oxidative stress was mediated through regulation of FOXO1/HNF4α complex binding to the C3 promoter. We identified a novel cluster of FOXO1 binding sites in the distal region of the C3 promoter that was essential for regulation of C3 expression by FOXO1/HNF4α complex. Further, activation of the main MAP kinase cascades (ERK1/2, p38, and JNK), AMP kinase and the transcription factor NF-κB were necessary for suppression of C3 during oxidative stress. Together, we identified molecular mechanisms and transcription factors that mediate suppression of C3 production in HepG2 cells during oxidative stress.
Keywords
компонент комплемента С3 окислительный стресс пероксид водорода FOXO1 HNF4α клетки гепатомы HepG2
Date of publication
31.01.2026
Year of publication
2026
Number of purchasers
0
Views
75

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