• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.570-576
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• 2019

Particulate matter (PM), which refers to the mixture of particles present in the air, can have harmful effects. Damage to cells by PM, including disruption of organelles and proteins, can trigger autophagy, and the relationship between autophagy and PM has been well studied. However, the cellular regulators of PM-induced autophagy have not been well characterized, especially in keratinocytes. The Aryl Hydrocarbon Receptor (AhR) is expressed in the epidermis and is activated by PM. In this study, we investigated the role of the AhR in PM-induced autophagy in HaCaT cells. Our results showed that PM led to AhR activation in keratinocytes. Activation of the AhR-target gene CYP1A1 by PM was reduced by co-treatment with ${\alpha}$-naphthoflavone (${\alpha}-NF$), an AhR inhibitor. We also evaluated activation of the autophagy pathway in PM-treated keratinocytes. In HaCaT cells, treatment with PM treatment led to the induction of microtubules-associated proteins light chain 3 (LC3) and p62/SQSTM1, which are essential components of the autophagy pathway. To study the role of the AhR in mediating PM-induced autophagy, we treated cells with ${\alpha}-NF$ or used an siRNA against AhR. Expression of LC3-II induced by PM was decreased in a dose dependent manner by ${\alpha}-NF$. Furthermore, knockdown of AhR with siAhR diminished PM-induced expression of LC3-II and p62. Together, these results suggest that inhibition of the AhR decreases PM-induced autophagy. We confirmed these results using the autophagy-inhibitors BAF and 3-MA. Taken together, our results indicate that exposure to PM induces autophagy via the AhR in HaCaT keratinocytes.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.65-70
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• 2004

Modulation of biotransformation enzymes is one mechanism by which a diet high in fruits and vegetable may influence cancer risk. Inhibition of cytochrome P450s (CYP) and concomitant induction of conjugating enzymes are hypothesized to reduce the impact of carcinogens in humans. Thus, exposure to types and amounts of phytochemicals may influence disease risk. Like other xenobiotics, many classes of phytochemicals are rapodly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. In humans, circulating phytochemical levels very widely among individuals even in response to controlled dietary interventions. Polymorphisms in biotransformation enzymes, such as the glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and sulfotransferases (SULT), may ocntribute to the variability in phytochemical clearance and efficacy; polymorphic enzymes with lower enzyme activity prolong the half-lives of phytochmicals in vivo. Isothiocyanates (ITC) in cruciferous vegetables are catalyzed by the four major human GSTs: however reaction velocities of the enzymes differ greatly. In some observational studies of cancer, polymorphisms in the GSTMI and GSTTI genes that result in complete lack of GSTM1-1 protein, respectively, confer greater protection from cruciferous vegetable in individuals with these genotypes. Similarly, we have shown in a controlled dietary trial that levels of GST-alpha-induced by ITC-are higher in GSTMI-null individuals exposed to cruciferous vegetablse. The selectivity of glucuronosyl conjugation of flavonoids is dependent both on flavonoid structure as well as on the UGI isozyme involved in its conjuagtion. The effects of UGI polymorphisms on flavonoid clearnace have not been examind; but polymorphisms affect glucuronidation of several drugs. Given the strong interest in the chemopreventive effects of flavonoids, systematic evaluation of these polymorphic UGTs and flavonoid pharmacokinetics are warranted. Overall, these studies suggest that for phytochemicals that are metabolized by, and affect activity of, biotransformation enzymes, interactions between genetic polymorphisms in the enzymes and intake of the compounds should be considered in studies of cancer risk. Genetic polymorphisms in biotransformation enzymes may account in prat for individual variation in metabolism of a wide range of phytochemicals and their ultimate impact on health.

• Preventive Nutrition and Food Science
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• v.16 no.3
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• pp.242-247
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• 2011

The methanolic extract of Rosa davurica Pall. roots exhibited strong antioxidant activity in a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay and was found to be a dose-dependent inhibitor of non-enzymatic formation of advanced glycation end products (AGEs), which are relevant to diabetes complications. HPLC-diode array detector (DAD) analysis of the R. davurica Pall. root extract led to the identification of four compounds: hydrocaffeic acid, catechin, epicatechin, and ellagic acid. Catechin was present in the largest amount and exhibited high antiglycation activity. A CYP3A4 assay was used to investigate potential interactions between drugs and the extract, and results suggest that the R. davurica Pall. root extract had moderate potential for interfering with drug metabolism. The R. davurica Pall. extract did not display anti-inflammatory activity on the level of that for tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in a lipopolysaccharide (LPS)-stimulated macrophage assay; however, the extract did exhibit low to moderate immunostimulatory activity in a pro-inflammatory macrophage assay. Therefore, we conclude that R. davurica Pall. root is a promising anti-AGE agent with low to moderate risks of associated inflammation or drug interaction.