Chain Breaker Research Articles

Anti-glycation and phytochemical properties of cinnamon stem-bark water extract

The study evaluated the ability of cinnamon stem-bark water extract (CWE) to break established cross-links formed between proteins and advanced glycation end-products (AGEs) as well as its anti-glycation effect. The extract showed a dose-dependent anti-glycation effect against total fluorescent AGEs (FAGEs) derived from both glucose and fructose. CWE recorded a uniform IC50 value of 0.13 mg/mL for both glucose and fructose-derived FAGEs while aminoguanidine, a well-known synthetic anti-glycative agent gave IC50 values of 0.14 mg/mL for the glucose and 0.17 mg/mL for the fructose derived FAGEs. The anti-glycative effect of CWE was also significantly higher than aminoguanidine against total immunogenic AGE (TIAGEs) in both sugar models (p < 0.001). While CWE and aminoguanidine showed weak protein cross-link breaking activity selectively on fructose-derived protein cross-links already formed, none whatsoever was detected exerted on the established glucose-derived protein cross-links. Phytochemical screening revealed the presence of several important secondary metabolites which may have contributed to the anti-glycative effect of CWE. Gas chromatography mass spectrometry enabled the identification of (+)-alpha-tocopherol acetate, a chain breaker, in the methanol fraction of CWE. Although CWE showed great potential for inhibition of formation of major types of AGEs, it appears to be poor in breaking established cross-links formed between proteins and AGEs.

Feminism as Depicted in Mahfouz’s Palace Walk, Gordimer’s None to Accompany Me, and Coetzee’s Disgrace

Feminism is among the common practices in the modern world and aims to proclaim gender equality. Mahfouz, Coetzee, and Gordimer are among the African Noel laureates who pioneered what could be termed a rebellion toward normality. Amina, a protagonist of Palace Walk, presents a character who purposes to challenge the biased and male-centric conventions. For instance, her choice of going to the mosque alone, in the absence of her husband, was a practice that was not acceptable in the Muslim culture; nevertheless, she took the bold step. On the other hand, Lucy is presented as a chain breaker who goes against the system of oppression by choosing a black husband. The choice of Lucy to leave her husband and start living with Rapulana, who was a black man, was a courageous move, and from that angle, she can be depicted as an agent of change. The same character is portrayed in Vera, who betrays her husband for another man, Ben – it is worth noting that Vera chose a black man, thus entering into an interracial relationship as in Lucy’s case. Such characters played a significant role in challenging what has been termed normalThe use of art presents a new perception of fighting for women’s rights non-violently. This study aims at answering questions on what causes gender inequality and how art, such as the use of novels, can be used to end this social issue.

Legal Protection for Traffic Police in Handling The Covid-19 Pandemic

This article aims to analyze the legal aspects of the traffic police's police in handling the covid-19 pandemic related to the legal basis of the traffic police's actions and analyze the legal protection of the traffic police who act as the Covid-19 chain breaker. Through normative legal research related to the legal aspects of traffic police actions as a Covid-19 chain breaker. In this study, the author uses a type of research, namely normative legal research. Normative research is research conducted by examining library materials or secondary data consisting of primary legal materials, secondary legal materials, and tertiary legal materials from each normative law. The findings from this study include: The juridical basis for the traffic police to break the Covid-19 chain is Article 13 of Law Number 2 of 2002 concerning the Police, Law Number 22 of 2009 on Road Traffic and Transportation, Government Regulation Number 21 of 2020 concerning Large-Scale Social Restrictions (PSBB), Decree of the Indonesian National Police Number MAK/2/III/2020 concerning Compliance with Government Policies in Handling the Corona Virus, and Police Telegram Letters. The Traffic Police during Covid-19 acted according to the law in accordance with Article 19 of Law No. 2 of 2002 concerning the Police and Article 10 of Indonesian Republic Police No. 8 of 2009 concerning the Implementation of Human Rights Principles and Standards in Discharging the Duties of the Indonesian National Police.

The Impact of COVID-19 Pandemic on Café Design Concept

Indonesia is one of the countries that have confirmed cases of COVID-19 since March 11, 2020. Where all sectors are mainly engaged in the culinary and hospitality industry due to the implementation of Pembatasan Sosial Berskala Besar (PSBB) that there are health protocol rules implemented by the government and a new adjustment to the building concept design. Café shall make innovation to survive from this pandemic. The research method used direct physical observation and literature studies. So that it can be seen the design concept that is feasible in this New Normal. The results of this study indicate that the café design concept has changed in accordance with the application of health protocols in the New Normal so as to create a building that is able to adapt to new habits that keep social activities safe during the pandemic. The main concept applied is the application of open space concept in a building and technology that can support cafe facilities. In the use of this open space concept, apart from creating larger open spaces, more openings, for the sake of circulation and lighting, touchless sensor technology, and layout of furniture designs to produce a design concept in a café. Accordance with the conditions of the COVID-19 pandemic. Open space concept in the new normal period is to improve the quality of a building that is healthy and good in terms of aesthetics and functionality, but can still support the COVID-19 virus chain breaker program.

Legal Aspects of Actions of the Traffic Police as a Chain Breaker for Covid-19 Transmission

The role of Police of the Republic of Indonesia in enforcing discipline among the community is very significant, especially the role of Traffic Police (SATLANTAS) in providing education to people who drive, use public transportation to access the public facilities and so on. However, people who want to be protected cannot accept the funeral of Covid-19 in their local cemeteries, by resisting police officers. So in this case, POLRI (the Police of the Republic of Indonesia) and especially the traffic polices play a significant role in facing the community. There is a need for legal protection for the efforts that the police will take in both preventive and repressive efforts. The purpose of this study is to analyze the Legal Aspects of traffic police action as a Covid-19 transmission chain breaker. The method used in this research is a normative juridical research method, which is research that focuses on examining the application of rules or norms in positive law. The purpose of this study is to analyze the legal aspects of traffic police action as a covid-19 chain breaker. This research is expected to provide information to the reader about the legal aspects of traffic police action as a Covid-19 chain breaker and a form of legal protection for traffic police who have a duty to break the covid-19 chain breaker. As for the results of this research, every action taken by the police, especially the traffic police during a pandemic to the public has a legal basis, namely Law Number 2 of 2002 on Police of the republic of Indonesia , Article 3 of Law Number 22 of 2009 traffic and road transport other the police also have a right to be protected like a civil society because they have the rights as stated in Article 28 of the 1945 Constitution and Article 10 of article number 8 of 2009 on the implementation of human rights principles and standards in the performance of the duties of the state police of the republic of Indonesia. So that for policyholders to be able to provide more strict regulations, and informative for the public and police officers can realize a common goal. It is hoped that no more similar cases will occur so that the public can better understand the rules in force in the Prevention of Covid-19 Transmission in Indonesia and the public can act more wisely in dealing with it.

Separation of proanthocyanidin polymers from American cranberries and predictive modeling of depolymerization using response surface methodology

About 85% of proanthocyanidins in the American cranberries are polymers with degree of polymerization above 4. These polymers have lower absorption rates and bioactivities than oligomers of smaller sizes. In the present study, proanthocyanidin polymers were separated from cranberries using a two-step chromatographic method and depolymerized into a mixture of monomers, dimers, trimers, and tetramers. Adding epicatechin as a chain breaker yielded 1659 mg oligomers per gram of polymers compared to a yield of 221 mg oligomers in the absence of epicatechin under predicted optimal conditions. Predictive modeling using response surface methodology showed that higher yields of oligomers were achieved at higher temperature and moderate acid concentration in the presence of epicatechin. Shorter reaction time and high acid concentration were favored in the absence of epicatechin. This research provided a practical approach to depolymerize proanthocyanidin polymers and had the potential to increase bioavailability and bioactivity of proanthocyanidins in cranberry extracts. Practical applications Cranberry extracts containing bioactive proanthocyanidins are being used as dietary supplements for prevention of urinary tract infections and other chronic conditions. However, about 85% of cranberry proanthocyanidins are polymers with degree of polymerization above 4. These polymers are not absorbable, therefore, their bioactivities were much lower than oligomers of smaller sizes. This research provided a practical approach to separate proanthocyanidin polymers from cranberries and convert them to monomers, dimers, trimers, and tetramers with higher absorption rates than polymers.

Impact of Natural Antioxidants on Biological Systems

ABSTRACT:Free radicals are the unstable electron-deficient species that reacts with different molecules to gain stability and to eliminate their unpaired condition. Antioxidant molecules neutralizes the free radicals by donating their electrons and inhibits the unwanted oxidative reactions in biological system. The imbalance between antioxidants and free radicals generated oxidative stress which leads to severe impairment of the biological systems. The purpose of the present review is to highlight the beneficial role of naturally occurring antioxidant systems in minimizing the damage and maintaining the homeostasis in the biological system. Enzymatic and non-enzymatic antioxidants are the major classes of natural antioxidants which executes diverse functions in the biological system to provide defense against the destructive accumulating effects of ROS/RNS. Superoxide dismutase (SOD) are responsible for providing first line of defense to thebiological system, by converting the superoxide anion radical (O oˉ) into hydrogen 2 peroxide (H O ) which eventually converted into water and oxygen. Non-enzymatic 2 2 antioxidants either endogenous or exogenous provides numerous crucial mechanisms to quench the ROS/RNS in the biological system. Endogenous antioxidants inhibits lipid peroxidation in the cellular membranes while the exogenous antioxidants acts as chain breakers and terminates the oxidative chain reaction. It is significant to sustain the level of exogenous antioxidants in the body through diet so that the normal biological processes can be maintained at optimal levels.

The EFFECT OF THE COMBINATION OF THE SESAME OIL AND VITAMIN E TO IMPROVE ERYTHROCYTE MEMBRANE ON HYPERCHOLESTEROL RATS

Objective: The purpose of this study was to determine the combination effect of sesame oil and vitamin E to the number of abnormal erythrocytes, and MDA levels by the amount of hemolysis. Hypercholesterolemia that is grown by erythrocyte membranes were decreased conditions that leads to atherosclerosis associated with oxidative stress which leads to lipid peroxidation. Sesame oil (SO) has special antioxidants that also contains 85% unsaturated fatty acid, where 40% consists of poly unsaturated fatty acid. Vitamin E is a chain breaker antioxidant that prevents the multiplication of free radical reactions in phospholipids.
 Methods: This research using 6 treatment groups, 3 groups received an atherogenic diet, while the other 3 groups received an atherogenic diet and treated with a combination of sesame oil with the same dose, added with 0.02 ml of vitamin E.
 Results: The results showed that the proportion of 1.2 ml SO and 0.02 ml of vitamin E, with the average amount (%) of hemolysis at 0.45% NaCl concentration was (5, 05 ±0.129), while in the control (33,87–1,919). The number (%) of erythrocytes is not normal (25,75± 2,473) while in the control (80,27± 4,631). Erythrocyte MDA level (0.229±0.039) µlmol / ml, while in the control (0.443 ± 0.013) µmol / ml.
 Conclussion: This research shows that the combination of oil and vitamin E had a significant decrease in the number of abnormal erythrocytes, the amount of hemolysis and MDA levels. The MDA reduction is followed by a decrease in the number of abnormal erythrocytes and the amount of hemolysis.

Narcotics Addicted Based on Constitution No. 35 of 2009 about Narcotics

Incipience of the constitution No. 35 of 2009 on narcotics are the most tend to be more humanist / humane in view of victims of drug abuse, but very hard on the dealers, importers and manufacturers of the drug itself. Moreover, the law is also confirmed for the addicts who are of age and their parents / guardians of the addicts who are not old enough for a mandatory report to health centers, hospitals or institutions medical and social rehabilitation are appointed by the government, to get a recovery or rehabilitation. Through the experience where in the world that has grown up to be an addict stigma society's belief that drug addicts are evil. Stigma is only made increasingly decline addicts. The enactment of constitution No. 35 of 2009 on narcotics provide fresh air to the shifting treatment of drug addicts. They are the victims that must be cured with the loving support. Supreme Court Circular (SEMA) No. 4 of 2010 and reinforced by SEMA No. 3 of 2011 confirms that addicts narcotics were caught red-handed by the authorities, and proved to be the judge can impose criminal penalties to undergo medical and social rehabilitation at a rehabilitation have been determined. In accordance with constitution No 35 point 54 of 2009 on Narcotics, narcotics addicted shall undergo medical rehabilitation and social rehabilitation at a rehabilitation center for drug dependence. With medical rehabilitation and social rehabilitation are intended to restore and / or develop the physical, mental and social addicts, with the ultimate goal to heal addicts from the bondage of drug addiction, then this method will become a tool chain breaker cycle illicit trafficking (in contrast to the demand and supply) which was recently increased. So at the present time law enforcement officers should be able to decide whether an offender substance abuse was a criminal narcotics or just as a drug addict.

Novel proanthocyanidin dimer analogues with the C-ring-opened diaryl-propan-2-gallate structural unit and enhanced antioxidant activities

This study aimed to establish an approach for preparing new representative proanthocyanidin oligomers from persimmon for further structure−activity relationship study. Persimmon tannins (with a mean degree of polymerization of 23.7) were depolymerized, using 0.1 M methanolic HCl, with (+)-catechin and (−)-epigallocatechin gallate as chain breakers. Normal phase high-performance liquid chromatography (NP−HPLC) coupled with reversed phase high-performance liquid chromatography mass spectrometry (RP−HPLC−MS) method was used to analyse the degradation products. Four B-type and one A-type dimers were tentatively identified. In addition, three dimer analogues, 1-(3′,4′-dihydroxyphenyl)-3-(2′′,4′′,6′′-trihydroxyphenyl)propan-2-ol-(epi)catechin dimer (B-type) and 1-(3′,4′,5′-trihydroxyphenyl)-3-(2′′,4′′,6′′-trihydroxyphenyl)-propan-2-gallate-(epi)gallocatechin-3-gallate dimers (A- and B-type), were reported for the first time. Three different assays were employed to evaluate the antioxidant capacities of the new dimer analogues. Our results revealed that the formation of the C-ring-opened diaryl-propan-2-gallate structural unit on dimer analogues enhanced their antioxidant abilities in aqueous systems for the first time. This research provided a workable approach for preparing novel dimeric proanthocyanidins for further structure–activity relationship study.

ChemInform Abstract: The Role of Antioxidants in the Chemistry of Oxidative Stress: A Review

AbstractReview: 303 refs.

Influence of the nature of the chain breaker on the thermal stability of phthalic anhydride-based polyesters

This study presents the synthesis of polyesters obtained from phthalic anhydride as acidic components and one mixture of monoethylene glycol and monohydric alcohol (in ratio 1.1:0.15). Molar ratio of the acid component and alcohol component was 1:1.25. n-Propanol, n-butanol, n-octanol and isoamyl alcohol were used as monohydric alcohol. Physicochemical characterization was performed by elemental analysis, FTIR/UATR spectroscopy of polyesters and char, EGA (evolved gas analysis), thermal analysis in synthetic air and in nitrogen atmosphere.

Depolymerization of cranberry procyanidins using (+)-catechin, (−)-epicatechin, and (−)-epigallocatechin gallate as chain breakers

Procyanidin dimers, trimers, and tetramers are absorbable, whereas larger oligomers are not. Procyanidins in cranberries are bioactive components that help prevent chronic diseases; however, 85% of cranberry procyanidins are large oligomers or polymers with a degree of polymerization above four. The objective of this study was to depolymerize cranberry procyanidins, particularly the polymers, into absorbable oligomers. Partially purified cranberry procyanidins (PCP) were obtained using chromatographic methods. The resultant extract contained predominant polymers with a degree of polymerization above ten (77.2% w/w). The extract was depolymerized, using 0.1 or 1M methanolic HCl, with (+)-catechin, (−)-epicatechin, or (−)-epigallocatechin gallate (EGCG) added as chain breakers. Depolymerization converted polymers into A-type and B-type dimers, trimers and tetramers. Use of EGCG as a chain breaker resulted in A- and B-type oligomers with EGCG as a terminal unit, indicating that the added flavan-3-ol attached to the C4 carbocations from procyanidins during depolymerization. The yield of B-type oligomers was higher than that of A-type oligomers. The yield increased when higher amounts of flavan-3-ols were used for depolymerization. EGCG, as a chain breaker, produced fewer procyanidin oligomers than did catechin or epicatechin. This research provided a practical approach that may enhance the bioavailability and bioactivity of procyanidins in cranberries.

Chain Breakers—A Survey of Fatal Ship Accidents With the Event-Chain Method

The ship research project DESSO (Design for Survival Onboard) aims at improving the safety of RO/RO (roll-on/roll-off) ferries. The project was organized in the autumn of 2003 in order to use the research and development resources existing in Sweden, combined with international expertise, for a radical RO/RO concept with a focus on safety. One part in the early stages of this project was to identify chain breakers from previous accidents, that is, something that would have prevented, stopped, or reduced the conse-quences of the incident event, in order to obtain a realistic basis of "working on the right problem." A systematic and in-depth analysis of a few selected significant and well-documented disasters was made using the event-chain method. The identified chain breakers were further categorized and analyzed to find ideas and concepts that would prevent these events from occurring. These efforts were further developed into a method where the graphics of event chains with chain breakers are used in workshops with experts in two stages. In general, it was found that "Management" in most cases was the initial cause of the events. Often, "Management" was also the reason for the continuing or worsening of the events. As such, education/training and stricter routines were found to be the most effective methods for reducing accidents and are at the same time an inexpensive measure to take. This, together with online stability calculations and decision-support systems, would have prevented most of the accidents analyzed in this work.

Conjugated autoxidizable triene (CAT) assay: A novel spectrophotometric method for determination of antioxidant capacity using triacylglycerol as ultraviolet probe

Described here is a novel spectrophotometric method for estimating antioxidant capacity in a 96-well microplate using as UV probes the conjugated triene triacylglycerols (TAGs) naturally present in tung oil. The TAGs of this commercially available oil contain around 86% eleostearic acid, an octadecatrienoic acid with conjugated trienes exhibiting strong UV absorption at 273 nm. In an oil-in-water emulsion at 37 °C, the azo initiator 2,2′-azobis(2-amidinopropane) dihydrochloride generated a constant flux of peroxy radicals, which destroyed the conjugated trienes. The absorbance decay at 273 nm, related to oxidative degradation of conjugated triene TAGs, was monitored in the absence and presence of various concentrations of antioxidants. To validate this new method, the antioxidant capacity of four phenolic compounds (gallic acid, (–)-epicatechin, chlorogenic acid, and rosmarinic acid) was measured using an area-under-the-curve calculation and expressed as Trolox equivalents, the value for Trolox being taken as reference. The order of efficacy was found to be rosmarinic acid > chlorogenic acid ∼ epicatechin > Trolox > gallic acid, which can be partially explained by the number of catecholic moieties and the polarity of these antioxidants. Moreover, the conjugated autoxidizable triene (CAT) assay provided good insight into antioxidant behavior (i.e., retarder or chain breaker). The same molecules were then analyzed in 2,2-diphenyl-1-picrylhydrazyl and fluorescein-based oxygen radical absorbance capacity assays, and the results are discussed critically with respect to those obtained with the CAT assay. This new method may constitute an easy-to-use, sensitive, and high-throughput in vitro protocol for evaluation of the antioxidant capacity of pure molecules and natural extracts in lipid oxidation.

Mitochondrial electron transport chain activity is not involved in ultraviolet A (UVA)-induced cell death

Ultraviolet A (UVA), the long wavelength part of the sun's ultraviolet radiation, elicits its harmful effects through production of reactive oxygen species. In this study, we have tested the hypothesis that the mitochondrial electron transport chain, the main source of reactive oxygen species in cells, importantly contributes to UVA-induced cell damage. Model cell lines completely lacking a mitochondrial electron transport chain (ρ 0-cells) were not protected against UVA-induced cell death. Also, primary human fibroblasts and keratinocytes with induced depletion of electron transport chain activity were not better protected against UVA-induced cell death. On the other hand, diphenyleneiodonium and resiniferatoxin, inhibitors of plasma membrane oxidases, protected primary human fibroblasts against UVA, as potently as the lipid peroxidation chain breaker Trolox. These data indicate that plasma membrane electron transport systems, but not the mitochondrial electron transport chain, play a major role in UVA-induced cell death.

Alternative pathways as mechanism for the negative effects associated with overexpression of superoxide dismutase

One of the most important antioxidant enzymes is superoxide dismutase (SOD), which catalyses the dismutation of superoxide radicals to hydrogen peroxide. The enzyme plays an important role in diseases like trisomy 21 and also in theories of the mechanisms of aging. But instead of being beneficial, intensified oxidative stress is associated with the increased expression of SOD and also studies on bacteria and transgenic animals show that high levels of SOD actually lead to increased lipid peroxidation and hypersensitivity to oxidative stress. Using mathematical models we investigate the question how overexpression of SOD can lead to increased oxidative stress, although it is an antioxidant enzyme. We consider the following possibilities that have been proposed in the literature: (i) Reaction of H 2O 2 with CuZnSOD leading to hydroxyl radical formation. (ii) Superoxide radicals might reduce membrane damage by acting as radical chain breaker. (iii) While detoxifying superoxide radicals SOD cycles between a reduced and oxidized state. At low superoxide levels the intermediates might interact with other redox partners and increase the superoxide reductase (SOR) activity of SOD. This short-circuiting of the SOD cycle could lead to an increased hydrogen peroxide production. We find that only one of the proposed mechanisms is under certain circumstances able to explain the increased oxidative stress caused by SOD. But furthermore we identified an additional mechanism that is of more general nature and might be a common basis for the experimental findings. We call it the alternative pathway mechanism.

Leaps in the dark

Preface Introduction: The past really is another country PART I: FALLING FROM GRACE Introduction to Part I 1. Joseph Glanvill: scientific witch-finder 2. The man who made underpants for frogs 3. Pettenkofer's poisoned chalice PART II: EUREKA! REVISITED Introduction to Part II 4. Sir Isaac Newton and the meaning of light 5. Dr James Lind and the Navy's scourge 6. The destruction of Ignaz Semmelweis PART III: HEROES MADE TO MEASURE Introduction to Part III 7. Will the real Johann Weyer please stand up? 8. Philippe Pinel: the re-forging of a chain breaker PART IV: DO-IT-YOURSELF HEROES Introduction to Part IV 9. The first casualty of war 10. Rank hath its privileges Conclusion: The bigger picture Index

Antioxidant activity of olive phenols: mechanistic investigation and characterization of oxidation products by mass spectrometry

In this work, the antioxidant activity of olive phenols is first characterized by their stoichiometries n(tot)(number of radicals trapped per antioxidant molecule) and their rate constants for the first H-atom abstraction k(1) by the stable radical DPPH. It appears that oleuropein, hydroxytyrosol and caffeic acid have the largest k(1) values, whereas dihydrocaffeic acid, an intestinal metabolite of caffeic acid, is the best antioxidant in terms of n(tot). For phenols with a catechol moiety n(tot) is higher than two, implying an antioxidant effect of their primarily formed oxidation products. A HPLC-MS analysis of the main products formed in the AAPH-induced oxidation of olive phenols reveals the presence of dimers and trimers. With hydroxytyrosol and dihydrocaffeic acid, oligomerization can take place with the addition of water molecules.The antioxidant activity of olive phenols is then evaluated by their ability to inhibit the AAPH-induced peroxidation of linoleic acid in SDS micelles. It is shown that olive phenols and quercetin act as retardants rather than chain breakers like alpha-tocopherol. From a detailed mechanistic investigation, it appears that the inhibition of lipid peroxidation by olive phenols can be satisfactorily interpreted by assuming that they essentially reduce the AAPH-derived initiating radicals. Overall, olive phenols prove to be efficient scavengers of hydrophilic peroxyl radicals with a long lasting antioxidant effect owing to the residual activity of some of their oxidation products.

Overexpression of Phospholipid-hydroperoxide Glutathione Peroxidase in Human Dermal Fibroblasts Abrogates UVA Irradiation-induced Expression of Interstitial Collagenase/Matrix Metalloproteinase-1 by Suppression of Phosphatidylcholine Hydroperoxide-mediated NFκB Activation and Interleukin-6 Release

Phospholipid-hydroperoxide glutathione peroxidase (PHGPx) exhibits high specific activity in reducing phosphatidylcholine hydroperoxides (PCOOHs) and thus may play a central role in protecting the skin against UV irradiation-triggered detrimental long term effects like cancer formation and premature skin aging. Here we addressed the role of PHGPx in the protection against UV irradiation-induced expression of matrix metalloproteinase-1 (MMP-1). For this purpose, we created human dermal fibroblast cell lines overexpressing human PHGPx. Overexpression led to a significant increase in PHGPx activity. In contrast to a maximal 4.5-fold induction of specific MMP-1 mRNA levels in vector-transfected cells at 24 h after UVA irradiation, no MMP-1 induction occurred at any studied time point after UVA treatment of PHGPx-overexpressing fibroblasts. As interleukin-6 (IL-6) was earlier shown to mediate the UVA induction of MMP-1, we studied whether PHGPx overexpression might interfere with the NFkappaB-mediated IL-6 induction and downstream signaling. Using transient transfections of IL-6 promoter constructs containing NFkappaB binding sites, we observed a high induction of the reporter gene luciferase in vector-transfected control cells and a significantly lower induction in PHGPx-overexpressing fibroblasts following UVA irradiation. Consistently both UVA irradiation and treatment of fibroblasts with PCOOHs led to phosphorylation and nuclear translocation of the p65 subunit, whereas cells overexpressing PHGPx exhibited impaired NFkappaB activation, p65 phosphorylation, and nuclear translocation. In line with this, the PHGPx-overexpressing fibroblasts showed a reduced constitutive and UVA irradiation-induced IL-6 release. After incubating PHGPx-overexpressing cells with PCOOHs a reduced induction of IL-6 was observed. This together with the suppression of UVA irradiation-induced IL-6 release in the presence of Trolox, a chain breaker of PCOOH-initiated lipid peroxidation, indicates that UVA irradiation-induced PCOOHs and subsequent lipid peroxides initiate the NFkappaB-mediated induction of IL-6, which mediates the induction of MMP-1. Our finding is particularly relevant in light of the already available small molecule mimetics of PHGPx.