Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 µM, 4-hydroxynonenal (HNE) at 0.10 µM, trans-2-hexanal at 0.10 µM, and trans-2, 4-hexadienal at 0.05 µM, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 µM (toxic) by converting to 1, 4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.

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The Toll-like receptor 4 (TLR4)-mediated myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays an essential role in inflammation resulting from invading microbes. However, whether the signaling pathway is activated in the inflammatory reaction of cerebral ischemia-reperfusion and its mechanism is still unclear. In this experiment mice were randomly divided into sham group, ischemia/reperfusion group and TLR4-blocked group with different time points of reperfusion at 12, 24, 48 and 72 h . Mice cerebral ischemia was induced by occlusion of common carotid arteries (CCA) bilaterally. TLR4 signaling pathway was inhibited using specific anti-TLR4 binding protein to prevent TLR4 from interacting with its receptors. We determined the result of TLR4 antibodies-blocking and mice cerebral ischemia-reperfusion injuries by Western blot, and evaluated neuronal damage in the hippocampus. We also determined expression of TLR4 mRNA and MyD88 mRNA by in situ hybridization (ISH), activation of nuclear factor (NF)-k kB by electrophoretic mobility-shift analysis (EMSA), and expression of interrleukin (IL)-1b b protein by Western blot. The results demonstrated that TLR4-mediated MyD88-dependent signaling pathway activated by ischemia-reperfusion may be involved in the mechanism of ischemia-reperfusion through upregulation of NF-k kB, IL-1b b.