Extracellular HMGB1 protein is known to induce inflammatory responses leading to an inflammatory storm. The outbreak of the Severe Acute Respiratory Syndrome COVID-19 due to the SARS-CoV-2 virus has resulted in a huge health concern worldwide. Recent data revealed that plasma/serum HMGB1 levels of patients suffering from inflammation-mediated disorders-such as COVID-19, cancer, and autoimmune disorders-correlate positively with disease severity and vice versa. A late release of HMGB1 in sepsis suggests the existence of a wide therapeutic window for treating sepsis. Rapid and accurate methods for the detection of HMGB1 levels in plasma/serum are, therefore, of great importance for monitoring the occurrence, treatment success, and survival prediction of patients with inflammation-mediated diseases. In this review, we briefly explain the role of HMGB1 in the cell, and particularly the involvement of extracellular HMGB1 (released from the cells) in inflammation-mediated diseases, with an emphasis on COVID-19. The current assays to measure HMGB1 levels in human plasma-Western blotting, ELISA, EMSA, and a new approach based on electrochemical immunosensors, including some of our preliminary results-are presented and thoroughly discussed.

• Klíčová slova
• COVID-19, ELISA, EMSA, HMGB1, immunosensor, plasma/serum,
• MeSH
• biosenzitivní techniky MeSH
• COVID-19 * krev   diagnóza   MeSH
• imunoanalýza MeSH
• lidé MeSH
• prognóza MeSH
• protein HMGB1 * krev   MeSH
• SARS-CoV-2 MeSH
• sepse * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• HMGB1 protein, human MeSH Prohlížeč
• protein HMGB1 * MeSH

HMGB1 protein and linker histone H1 have overlapping binding sites in the nucleosome. HMGB1 has been implicated in many DNA-dependent processes in chromatin involving binding of specific proteins, including transcription factors, to DNA sites pre-bent by HMGB1. HMGB1 can also act as an extracellular signaling molecule by promoting inflammation, tumor growth a metastasis. Many of the intra- and extracellular functions of HMGB1 depend on redox-sensitive cysteine residues of the protein. Here we report that mild oxidization of HMGB1 (and much less mutation of cysteines involved in disulphide bond formation) can severely compromise the functioning of the protein as a DNA chaperone by inhibiting its ability to unwind or bend DNA. Histone H1 (via the highly basic C-terminal domain) significantly inhibits DNA bending by the full-length HMGB1, and the inhibition is further enhanced upon oxidization of HMGB1. Interestingly, DNA bending by HMGB1 lacking the acidic C-tail (HMGB1ΔC) is much less affected by histone H1, but oxidization rendered DNA bending by HMGB1ΔC and HMGB1 equally prone for inhibition by histone H1. Possible consequences of histone H1-mediated inhibition of DNA bending by HMGB1 of different redox state for the functioning of chromatin are discussed.

• MeSH
• cystein genetika   metabolismus   MeSH
• histony chemie   genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• molekulární modely MeSH
• mutace MeSH
• nukleozomy MeSH
• oxidace-redukce MeSH
• protein HMGB1 chemie   genetika   metabolismus   MeSH
• superhelikální DNA metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystein MeSH
• Hbp1 protein, rat MeSH Prohlížeč
• histony MeSH
• nukleozomy MeSH
• protein HMGB1 MeSH
• superhelikální DNA MeSH