Deok Kun Oh

Multistep Enzymatic Synthesis of Long-Chain α,ω-Dicarboxylic and ω-Hydroxycarboxylic Acids from Renewable Fatty Acids and Plant Oils†

A multistep enzyme catalysis was successfully implemented to produce long-chain α,ω-dicarboxylic and ω-hydroxycarboxylic acids from renewable fatty acids and plant oils. Sebacic acid as well as ω-hydroxynonanoic acid and ω-hydroxytridec-11-enoic acid were produced from oleic and ricinoleic acid.

20‐O‐β‐d‐Glucopyranosyl‐20(S)‐Protopanaxadiol Suppresses UV‐Induced MMP‐1 Expression Through AMPK‐Mediated mTOR Inhibition as a Downstream of the PKA‐LKB1 Pathway

Various health effects have been attributed to the ginsenoside metabolite 20‐O‐β‐D‐glucopyranosyl‐20(S)‐protopanaxadiol (GPD); however, its effect on ultraviolet (UV)‐induced matrix metalloproteinase (MMP)‐1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV‐induced MMP‐1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV‐induced MMP‐1 expression in HDFs and suppressed the UV‐induced phosphorylation of mammalian target of rapamycin (mTOR) and p70S6K without inhibiting the activity of phosphatidylinositol 3‐kinase and Akt, which are well‐known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate‐activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5‐aminoimidazole‐4‐carboxamide‐1‐β‐d‐ribofuranosyl 5′‐monophosphate (AICAR), an activator of AMPK, augmented UV‐induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP‐1 expression. AICAR also decreased the phosphorylation of mTOR and p70S6K. However, compound C, an antagonist of AMPK, increased MMP‐1 expression. In HDF cells with AMPK knock‐down using shRNA, MMP‐1 expression was increased. These results indicate that AMPK activation plays a key role in MMP‐1 suppression. Additionally, the cAMP‐dependent protein kinase (PKA) inhibitor, H‐89, antagonized GPD‐mediated MMP‐1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV‐induced MMP‐1 expression is due to the activation of AMPK as a downstream of the PKA‐LKB1 pathway. J. Cell. Biochem. 115: 1702–1711, 2014.

IL-32θ negatively regulates IL-1β production through its interaction with PKCδ and the inhibition of PU.1 phosphorylation

It has been well known that IL‐32 exerts pro‐inflammatory effects on the various inflammatory diseases in clinical studies. Here, we confirmed that IL‐32θ, a new isoform of IL‐32, decreased the phorbol 12‐myristate 13‐acetate (PMA)‐induced IL‐1β expression in THP‐1 human myelomonocyte. We previously reported that the IL‐32 isoforms control expressions of other cytokines via novel PKCs. Likewise, IL‐32θ interacted with PKCδ, and consequently inhibited PKCδ‐mediated phosphorylation of PU.1. Moreover, IL‐32θ attenuated the localization of PU.1 into the IL‐1β promoter region. These findings reveal that IL‐32θ reduces PKCδ‐mediated phosphorylation of PU.1, resulting in attenuation of IL‐1β production.

PKCι is a target of 7,8,4′-trihydroxyisoflavone for the suppression of UVB-induced MMP-1 expression

The soy isoflavone daidzein is bioconverted to 7,8,4′‐trihydroxyisoflavone (7,8,4′‐THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)‐1 inhibitory properties of 7,8,4′‐THIF that arise through the suppression of UVB‐induced MMP‐1 expression. 7,8,4′‐THIF reduced UVB‐induced MMP‐1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB‐induced transcriptional activity of AP‐1, a major activator of MMP‐1 expression. Additionally, it was observed that the mitogen‐activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP‐1 expression, was suppressed by 7,8,4′‐THIF. Protein kinase C iota (PKCι) was suspected to be a direct target of 7,8,4′‐THIF. The direct interaction between 7,8,4′‐THIF and PKCι was confirmed using pull‐down assays and immobilized metal ion affinity‐based fluorescence polarization assays. Finally, we observed that 7,8,4′‐THIF inhibited UVB‐induced MMP‐1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4′‐THIF, a bioconversion product of daidzein, suppresses UVB‐induced MMP‐1 expression.