Question

In the background section the authors wrote “The extracelluar activities of HMGB1 depend on the redox state of HMGB1 resulting in activation of different HMGB1 receptors.” What is the redox state of HMGB1 as written in the quote? (1 point)

In the background section the authors wrote “During inflammation, all-thiol HGMB1may be oxidized to the disulfide form of HGMB1, which then binds to Toll-like receptor 4 (TLR4) to induce cytokine production.” What kind of agent does this make all-thiol HGMB1? (1 point)

Is HGMB1 a cell surface receptor? (1 point)

How do you know that your answer to question 3 is correct? (1 point)

In the results section the authors wrote “Figure 1d shows that 5 µg (n = 5) of disulfide HMGB1 resulted in significant mechanical hypersensitivity of abdominal/perineal area only with the highest filament tested (0.07 g; Fig. 1d). Higher doses of disulfide HMGB1 10 (n = 6) or 20 µg (n = 3) significantly increased von Frey responses compared to baseline for all filaments tested (Fig. 1e, f).” What redox form is disulfide HGMB1? (1 point)

In the results section the authors wrote “In contrast, intravesical all-thiol HMGB1 did not cause any change in abdominal mechanical hypersensitivity for any of the doses tested (Fig. 1g-k).” What redox form is all-thiol HMGB1? (1 point)

Was the reduced and oxidized form of HMGB1 different for micturition volume? (1 point)

Was the reduced and oxidized form of HMGB1 different for micturition frequency? (1 point)

Was the reduced and oxidized form of HMGB1 different for inflammation? (1 point)

Was the reduced and oxidized form of HMGB1 different for edema and stromal reactive changes? (1 point)

Reference: https://bmcphysiol.biomedcentral.com/articles/10.1186/s12899-017-0032-9

Answer 1

What redox form is disulfide HGMB1?

The High Mobility Group B1 (HMGB1) protein plays important roles in both intracellular (reductive) and extracellular (oxidative) environments. We have carried out quantitative investigations of the redox chemistry involving Cys22 and Cys44 of the HMGB1 A-domain, which form an intramolecular disulfide bond. Using NMR spectroscopy, we analyzed the real-time kinetics of the redox reactions for the A-domain in glutathione and thioredoxin systems, and also determined the standard redox potential. Thermodynamic experiments showed that the Cys22-Cys44 disulfide bond stabilizes the folded state of the protein. These data suggest that the oxidized HMGB1 may accumulate even in cells under oxidative stress