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1.
ChemMedChem ; 13(3): 227-230, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29286587

RESUMO

In recent years there has been a clear consensus that neurodegenerative conditions can be better treated through concurrent modulation of different targets. Herein we report that combined inhibition of transglutaminase 2 (TG2) and histone deacetylases (HDACs) synergistically protects against toxic stimuli mediated by glutamate. Based on these findings, we designed and synthesized a series of novel dual TG2-HDAC binding agents. Compound 3 [(E)-N-hydroxy-5-(3-(4-(3-oxo-3-(pyridin-3-yl)prop-1-en-1-yl)phenyl)thioureido)pentanamide] emerged as the most interesting of the series, being able to inhibit TG2 and HDACs both in vitro (TG2 IC50 =13.3±1.5 µm, HDAC1 IC50 =3.38±0.14 µm, HDAC6 IC50 =4.10±0.13 µm) and in cell-based assays. Furthermore, compound 3 does not exert any toxic effects in cortical neurons up to 50 µm and protects neurons against toxic insults induced by glutamate (5 mm) with an EC50 value of 3.7±0.5 µm.


Assuntos
Amidas/síntese química , Proteínas de Ligação ao GTP/antagonistas & inibidores , Inibidores de Histona Desacetilases/síntese química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/síntese química , Piridinas/síntese química , Tioureia/análogos & derivados , Tioureia/síntese química , Transglutaminases/antagonistas & inibidores , Amidas/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Simulação de Acoplamento Molecular , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Ligação Proteica , Proteína 2 Glutamina gama-Glutamiltransferase , Piridinas/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Tioureia/farmacologia
2.
Eur J Med Chem ; 139: 378-389, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28810189

RESUMO

Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aß), glycogen synthase kinase 3ß (GSK-3ß) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3ß (IC50 = 24.36 ± 0.01 µM) and Aß42 self-aggregation (IC50 = 9.0 ± 1.4 µM), to chelate copper (II) and to act as exceptionally strong radical scavenger (kinh = 6.8 ± 0.5 · 105 M-1s-1) even in phosphate buffer at pH 7.4 (kinh = 3.2 ± 0.5 · 105 M-1s-1). Importantly, compound 3 showed high-predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 µM and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cinamatos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Animais , Cinamatos/síntese química , Cinamatos/química , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Glicogênio Sintase Quinase 3 beta/metabolismo , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
3.
Medchemcomm ; 8(2): 338-345, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108749

RESUMO

Previous studies within our group have yielded a class of cinnamoyl-based competitive reversible inhibitors for tissue transglutaminase (TG2), with Ki values as low as 1.0 µM (compound CP4d). However, due to the electrophilic nature of their alkene moiety, this class of inhibitors is susceptible to nucleophilic attack by glutathione, a key element in cellular metabolism and toxicity response. To address this issue, we made several modifications to the inhibitor scaffold, ultimately showing that a bis(triazole) scaffold increased resistance to nucleophilic attack, with compound 27d being the most potent (Ki = 10 µM). In the process of reducing reactivity, we also prepared a new class of inhibitors, replacing the alkene of CP4d with an alkyne, leading to a significant increase in potency for compound 22b (Ki = 420 nM).

4.
Expert Opin Ther Pat ; 26(1): 49-63, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26560530

RESUMO

INTRODUCTION: Transglutaminases (TGases) are a class of enzymes that play multifunctional roles. Their protein-crosslinking activity has been linked to fibrosis and Huntington's disease, their glutamine deamidation activity has been related to celiac disease and their GTP-binding activity has been implicated in cancer. All of these physiological disorders have prompted the development of inhibitors, which has accelerated dramatically over the past decade. AREAS COVERED: This review presents an overview of TGase inhibitors published in the patent literature, from the first compounds developed in the late 1980's, to the current date. This article is focussed on the chemical structure of new inhibitors and their probable mechanism of action. EXPERT OPINION: Comparison of effective TGase inhibitors reveals common structural features that may guide future design. Many of these elements are embodied in the first TGase inhibitor to recently enter into clinical trials.


Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Transglutaminases/antagonistas & inibidores , Animais , Doença Celíaca/tratamento farmacológico , Doença Celíaca/enzimologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Humanos , Doença de Huntington/tratamento farmacológico , Doença de Huntington/enzimologia , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Patentes como Assunto , Transglutaminases/metabolismo
5.
Trends Pharmacol Sci ; 36(1): 32-40, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25500711

RESUMO

Tissue transglutaminase (TG2) catalyzes the cross-linking of proteins by the formation of isopeptide bonds between glutamine (Gln) and lysine (Lys) side chains. Although TG2 is essential for the stabilization of the extracellular matrix, its unregulated activity has been implicated in celiac disease, fibrosis, and cancer metastasis, among other disorders. Given the importance and range of TG2-related pathologies, recent work has focused on the development of potent and selective inhibitors against TG2. In this review, we present the latest and most noteworthy irreversible and reversible inhibitors of TG2, and offer perspectives for the design of future inhibitors, in the hope that lead compounds with therapeutic potential may soon be discovered.


Assuntos
Transglutaminases/antagonistas & inibidores , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Conformação Proteica , Transglutaminases/química , Transglutaminases/metabolismo
6.
Bioorg Chem ; 57: 186-197, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25035302

RESUMO

Tissue transglutaminase (TG2) is a calcium-dependent enzyme that catalyses several acyl transfer reactions. The most biologically relevant of these involve protein-bound Gln residues as an acyl-donor substrate, and either water or a primary amine as an acyl-acceptor substrate. The former leads to deamidation of Gln to Glu, whereas the latter leads to transamidation, typically resulting in protein cross-linking when the amine substrate is a protein-bound Lys residue. In this review, we present an overview of over fifty years of mechanistic studies that have led to our current understanding of TG2-mediated hydrolysis and transamidation.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Transglutaminases/metabolismo , Acilação , Animais , Proteínas de Ligação ao GTP/química , Humanos , Hidrólise , Modelos Moleculares , Conformação Proteica , Proteína 2 Glutamina gama-Glutamiltransferase , Especificidade por Substrato , Transglutaminases/química
7.
Environ Sci Pollut Res Int ; 20(12): 8717-28, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23728967

RESUMO

This study examines the characteristics of volatile organic compounds (VOCs) and their major emission sources at the Bulgwang site in Seoul, Korea. The annual levels of VOCs (96.2-121.1 ppb C) have shown a decreasing trend from 2004 to 2008. The most abundant component in Seoul was toluene, which accounted for over 23.5 % of the total VOCs on the parts per billion on a carbon basis, and the portions of alkanes with two to six carbons constituted the largest major lumped group, ranging from 40.1 to 48.4 % (45.3 ± 3.7 %) of the total VOCs. Major components of the solvent (toluene, m/p-xylene, o-xylene, and ethylbenzene) showed high in daytime and summer and low in nighttime and winter due mainly to the variation of the ambient temperature. The species mostly emitted from gasoline vapor (i/n-butane, i/n-pentane, n-hexane, and 2-methylpentane) and vehicular exhaust (ethylene, acetylene, and benzene) showed bimodal peaks in the diurnal variation around the commuting hours because of the high traffic volume. For the 14 out of 15 highest concentration species, the weekend effect was only evident on Sundays because of the stepwise implementation of the 5-day work-week system. Principal components analysis (PCA) was applied in order to identify the sources of the 15 highest concentration VOCs and, as a result, three principal components such as gasoline vapor (48.9 %), vehicular exhaust (17.9 %), and evaporation of solvents (9.8 %) were obtained to explain a total of 76.6 % of the data variance. Most influential contributing sources at the sampling site were traffic-related ones although the use of solvent was the dominant emission source based on the official emission inventory.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Compostos Orgânicos Voláteis/análise , República da Coreia , Estações do Ano , Emissões de Veículos/análise
8.
Environ Sci Pollut Res Int ; 20(3): 1468-81, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22886781

RESUMO

The characteristics of volatile organic compounds (VOCs) and their annual trends in Seoul, Korea were investigated, with their optimal control strategy suggested. The annual concentration of VOCs (96.2-121.1 ppbC) has shown a decreasing trend from 2004 to 2008, suggesting the control strategy via the "Special Measures for Metropolitan Air Quality Improvement," which was implemented in 2005, has been successful. The contributions of individual VOC to the production of ambient ozone and secondary organic aerosol (SOA) are discussed to assess the adequacy of current control strategies. The contribution of aromatics (C6-C10) to the production of ozone accounted for 38.7-46.3 % of the total ozone production, followed by low carbon alkanes (C2-C6) (27.0-35.9 %). The total SOA formation potential of VOCs was found to range from 2.5 to 3.5 µg m(-3), mainly as a result of aromatics (C6-C10) (over 85 %). Considering the contributions from ozone and SOA production, it was concluded that solvent use was the most important emission source, followed by vehicle exhaust emissions. Thus, the current emission control strategy focused on these two emission sources is appropriate to reduce the VOCs related pollution level of the Seoul Metropolitan Region. Still, an additional control strategy, such as controlling the emissions from meat cooking, which is an emission source of high carbon alkanes (C7-C10), needs to be considered to further reduce the VOCs related pollution level in Seoul.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Ozônio/análise , Compostos Orgânicos Voláteis/análise , Aerossóis/análise , Aerossóis/química , Poluentes Atmosféricos/química , Poluição do Ar/análise , Cidades , Monitoramento Ambiental , Ozônio/química , República da Coreia
9.
J Environ Manage ; 105: 138-43, 2012 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-22542982

RESUMO

To improve the air quality in the Seoul Metropolitan area (SMA), the Korean government has implemented special measures in the 1990s. As part of these measures, the Cap-and-Trade System (CATS) was introduced and executed in July 1, 2007 for the oxides of nitrogen (NOx) and sulfur (SOx) to provide added flexibility for large sources to meet the required emission reductions. However, the trade via the SMA CATS for the air pollutants has not been active because of the limited buyers and sellers within the system as well as limited tradable species. For more flexible operation of the SMA CATS, following strategies have been suggested and their merits are discussed; (1) to link the SMA CATS with the Korea Voluntary Emission Reduction (KVER) program which is a program to manage greenhouse gases (GHGs), and (2) to extend the system, such as extension of the tradable species, participants, and introducing a project-based certification mechanism for pollutants reduction.


Assuntos
Poluentes Atmosféricos/análise , Conservação dos Recursos Naturais/legislação & jurisprudência , Óxidos de Nitrogênio/química , Óxidos de Enxofre/química , Conservação dos Recursos Naturais/métodos , Monitoramento Ambiental/métodos , República da Coreia
10.
Int J Sports Med ; 24(2): 114-7, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12669257

RESUMO

The effect of treadmill exercise on cell proliferation in the dentate gyrus was studied in Sprague-Dawley rats via 5-bromo-2'-deoxyuridine (BrdU)-specific immunohistochemistry. For studying the dependence of this effect on the magnitude of exercise, animals were divided into the control, light-exercise, moderate-exercise, and severe-exercise groups; different exercise regimens were applied to the groups. To study the temporal dependence of this effect, animals were divided into the control, 1-day-exercise, 3-days-exercise, 7-days-exercise, 14-days-exercise, and 28-days-exercise groups; the regimen used on the light-exercise group was applied to each of the exercise group over the respective number of days. Cell proliferation was most prominent in the light-exercise group (p < 0.001) and reached a maximum level after 7 days of exercise (p < 0.001). In this study, it was shown that cell proliferation is modulated by the intensity and duration of treadmill exercise.


Assuntos
Giro Denteado/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Bromodesoxiuridina/metabolismo , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
11.
J Sports Med Phys Fitness ; 43(1): 99-104, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12629470

RESUMO

AIM: The duration-dependence of the effect of forced treadmill exercise on the immune system is a subject of ongoing research. In this study, the effect of forced treadmill exercise on immune responses was investigated by evaluating the lymphocyte subset fractions in the peripheral blood and spleen of Sprague-Dawley rats. EXPERIMENTAL DESIGN: Comparative investigation over 8 weeks. SETTING: Experimental animal laboratory. PARTICIPANTS: Male Sprague-Dawley rats 5 weeks of age, weighing 150+/-10 g. INTERVENTIONS: Animals were randomly assigned to one of the 4 following groups: the control group, the 1-week-exercise group, the 4-week-exercise group, and the 8-week-exercise group. MEASURES: Lymphocyte subset fractions, including those for T, B, CD4+, and CD8+ cells and the T/B and CD4+/CD8+ ratios in the peripheral blood and spleen were measured via flow cytometric analysis after treadmill exercise. RESULTS: The T cell and CD4+ cell fractions in both the peripheral blood and spleen were increased significantly after 8 weeks of treadmill exercise, but the B cell and CD8+ cell fractions did not change significantly. CONCLUSION: From the results of the present study, it is suggested that a period of one week is insufficient to eliminate the effects of exercise-induced stress, that 4 weeks are needed to return to the control state, and that at least 8 weeks are needed in order for exercise of moderate intensity to have a positive effect on the immune system.


Assuntos
Teste de Esforço , Condicionamento Físico Animal/métodos , Resistência Física/imunologia , Adaptação Fisiológica/imunologia , Animais , Citometria de Fluxo , Contagem de Linfócitos , Masculino , Ratos , Baço/imunologia , Tempo
13.
J Pharm Pharmacol ; 53(9): 1295-302, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11578113

RESUMO

The effects of 14 synthetic 2'-hydroxychalcone derivatives on prostaglandin E2 (PGE2) production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), were examined to clarify the structure-activity relationship. 2',4-Dihydroxy-4'-methoxychalcone (compound 3), 2',4-dihydroxy-6'-methoxychalcone (compound 8) and 2'-hydroxy-4'-methoxychalcone (compound 9) suppressed PGE2 production more potently than the other compounds. The IC50 (50% Inhibitory concentration) value for compounds 3, 8 and 9 was calculated to be 3 microM. The activity of cyclooxygenase (COX)-1 was inhibited slightly by compound 9, but that of COX-2 was not inhibited. At concentrations that inhibited the production of PGE2, compound 9 had no effect on the release of radioactivity from [3H]arachidonic acid-labelled macrophages stimulated by TPA. Western-blot analysis revealed that the induction of COX-2 protein by TPA was inhibited by compound 9 in parallel with the inhibition of PGE2 production. Compounds 3 and 8 had similar effects. These findings suggest that 4'-methoxyl and 6'-methoxyl groups are required for the expression of more potent inhibitory activity against PGE2 production, and that the inhibition of PGE2 production by these 2'-hydroxychalcone derivatives is due to the inhibition of TPA-induced COX-2 protein expression.


Assuntos
Chalcona/análogos & derivados , Chalcona/farmacologia , Dinoprostona/biossíntese , Animais , Western Blotting , Carcinógenos/farmacologia , Chalconas , Ciclo-Oxigenase 2 , Isoenzimas/biossíntese , Macrófagos Peritoneais , Masculino , Prostaglandina-Endoperóxido Sintases/biossíntese , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/farmacologia
14.
J Nat Prod ; 64(9): 1234-7, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11575965

RESUMO

Fractionation guided by immunomodulatory activity of the EtOAc extract of the Ascomycete Eupenicillium crustaceum has afforded two new naturally occurring products, 4'-oxomacrophorin D (1) and 4'-oxomacrophorin A (2), as the immunosuppressive components of this fungus [1: 3-hydroxy-3-methylglutaryl (HMG) conjugate of 2]. The structures including the absolute configurations of 1 and 2 have been determined on the basis of chemical correlation of 1 with macrophorin D (3). The absolute configuration of the HMG moiety in 3 has been revised from 3R to 3S.


Assuntos
Adjuvantes Imunológicos/isolamento & purificação , Ascomicetos/química , Imunossupressores/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Azatioprina/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Concanavalina A/farmacologia , Ciclosporina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Imunossupressores/química , Imunossupressores/farmacologia , Concentração Inibidora 50 , Japão , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Baço/citologia , Baço/efeitos dos fármacos , Estereoisomerismo , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Tacrolimo/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos
15.
Neurosci Lett ; 308(1): 25-8, 2001 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-11445277

RESUMO

Effect of caffeine on the expression of tryptophan hydroxylase (TPH), rate limiting enzyme of serotonin synthesis, in dorsal and median raphe was investigated via immunohistochemistry. In exercise groups, Sprague-Dawley rats were put on treadmill running for 30 min per day for 6 consecutive days. On the seventh day, animals of control-with-caffeine group were injected subcutaneously with 4 mg/kg caffeine, while control-without-caffeine group were injected with 0.9% NaCl, sacrificed 2 h later. Exercise-with-caffeine group and exercise-without-caffeine group were injected with caffeine and NaCl, respectively; all-out time was determined 1 h after injection, and then sacrificed. Caffeine increased all-out time in exercised rats, and inhibited the exercise-induced elevation in TPH expression. The suppressive effect of caffeine on TPH expression in exercised rats can be suggested as one possible ergogenic mechanism of caffeine.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Neurônios/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Núcleos da Rafe/efeitos dos fármacos , Serotonina/biossíntese , Triptofano Hidroxilase/efeitos dos fármacos , Animais , Teste de Esforço , Imuno-Histoquímica , Masculino , Neurônios/citologia , Neurônios/enzimologia , Condicionamento Físico Animal , Esforço Físico/fisiologia , Núcleos da Rafe/citologia , Núcleos da Rafe/enzimologia , Ratos , Ratos Sprague-Dawley , Triptofano Hidroxilase/metabolismo
16.
Planta Med ; 67(4): 362-4, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11458457

RESUMO

Platycodin D, isolated from the root of Platycodon grandiflorum A. DC. (Campanulaceae) suppressed prostaglandin E2 production at 10 and 30 microM in rat peritoneal macrophages stimulated by the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA). Platycodin D3 and oleanolic acid showed no effect at these concentrations. Western blot analysis revealed that the induction of COX-2 protein by TPA was inhibited by platycodin D in parallel with the inhibition of prostaglandin E2 production. Platycodin D showed no direct effect on COX-1 and COX-2 activities. TPA-induced release of [3H]arachidonic acid from pre-labeled macrophages was also not inhibited by platycodin D.


Assuntos
Células Cultivadas/efeitos dos fármacos , Dinoprostona/antagonistas & inibidores , Dinoprostona/metabolismo , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Raízes de Plantas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos , Animais , Ácido Araquidônico/metabolismo , Células Cultivadas/metabolismo , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Dexametasona/farmacologia , Dinoprostona/análise , Medicamentos de Ervas Chinesas/química , Indução Enzimática/efeitos dos fármacos , Indometacina/farmacologia , Isoenzimas/metabolismo , Macrófagos Peritoneais/metabolismo , Proteínas de Membrana , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Proteína Quinase C/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Saponinas/química , Acetato de Tetradecanoilforbol/farmacologia
17.
Environ Sci Technol ; 35(22): 4487-94, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11757606

RESUMO

A recently developed electron probe X-ray microanalysis (EPMA), called low-Z EPMA, employing an ultrathin window energy-dispersive X-ray detector, was applied to characterize aerosol particles collected at two sampling sites, namely, Kosan and 1100 Hill of Cheju Island, Korea, on a summer day in 1999. Since low-Z EPMA can provide quantitative information on the chemical composition of aerosol particles, the collected aerosol particles were classified and analyzed based on their chemical species. Many different particle types were identified, such as marine-originated, carbonaceous, soil-derived, and anthropogenic particles. Marine-originated particles, such as NaNO3- and Na2SO4-containing particles, are very frequently encountered in the two samples. In this study, it was directly proven that the observed nitrate particles were from sea salts. In addition, two types of nitrate particles from sea salts were observed, with and without Mg. The sodium nitrate particles without Mg were believed to be collected as crystalline form, either with the sodium nitrate particles being fractionally recrystallized within evaporating seawater drops or with recrystallized sodium chloride particles having reacted with gaseous nitrogen species in the air to form the crystalline sodium nitrate particles. The other seemed to be collected as seawater drops, where the atmospheric reaction had occurred in the droplets, and thus sodium as well as magnesium nitrates were observed. Carbonaceous particles are the most abundant in the samples at both sites. From this study, it was found that about three-quarters of the carbonaceous particles in the samples were biogenic, which partially explains a previously reported observation of a large concentration of organic carbon particles as compared to elemental carbon. Various soil-derived particles were also observed. In addition to aluminosilicate- and iron oxide-containing particles, which are ubiquitous components in soil-derived particles, CaCO3-, Al2O3- and Cr-containing particles were also frequently encountered.


Assuntos
Poluentes Atmosféricos/análise , Microanálise por Sonda Eletrônica/métodos , Monitoramento Ambiental/métodos , Nitratos/química , Cloreto de Sódio/química , Aerossóis/química , Microanálise por Sonda Eletrônica/normas , Coreia (Geográfico) , Magnésio/química , Tamanho da Partícula , Sensibilidade e Especificidade
18.
J Invest Dermatol ; 115(6): 1108-14, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11121149

RESUMO

Peroxiredoxins are a family of peroxidases that are ubiquitously and abundantly expressed in mammalian tissues; however, comparatively less is known about their expression in the skin. In this study, we examined the expression of three isotypes of peroxiredoxins (I-III) in rat skin. Western blot analyses showed strong expression of peroxiredoxins I-III in the epidermis and dermis of intact skin. Additionally, they were expressed in cultured rat keratinocytes and fibroblasts. Confocal image analyses revealed that peroxiredoxin II was present in the cytoplasm as a diffuse, reticulated pattern. In immunohistochemical staining of rat skin, peroxiredoxin expression was mainly localized to the epidermis, hair follicles, and sebaceous glands. In the epidermis, peroxiredoxins I and II were expressed in all layers with a gradient of increasing expression to the granular layer. In contrast, peroxiredoxin III was expressed in all layers with a gradient of expression decreasing to the granular layer. In the hair follicle, peroxiredoxins I-III were mainly expressed in the outer root sheath, except peroxiredoxin II, which was strongly expressed in the inner root sheath. In situ hybridization showed that mRNA expression was commensurate with the level of protein. Ultraviolet B radiation increased peroxiredoxin II expression in rat skin within 15 min after irradiation. From this study we conclude that peroxiredoxin isoforms are ubiquitously expressed in rat skin, and expression of at least peroxiredoxin II can be regulated by ultraviolet irradiation as a peroxidase in the skin. J Invest Dermatol 115:1108-1114 2000


Assuntos
Antioxidantes/metabolismo , Peroxidases/biossíntese , Pele/metabolismo , Animais , Especificidade de Anticorpos , Fibroblastos/química , Folículo Piloso/metabolismo , Isotipos de Imunoglobulinas/biossíntese , Isotipos de Imunoglobulinas/imunologia , Imuno-Histoquímica , Queratinócitos/química , Masculino , Peroxidases/genética , Peroxirredoxinas , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Pele/efeitos da radiação , Raios Ultravioleta
19.
Br J Dermatol ; 142(4): 653-9, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10792214

RESUMO

Ultraviolet (UV) irradiation is known to induce serious oxidative damage in the skin via lipid peroxidation. Nitric oxide (NO) synthesized by keratinocytes, melanocytes and endothelial cells in response to proinflammatory cytokines and UV radiation, has been reported to prevent UV-induced apoptosis in the skin. We have examined the effects of NO on UVB-induced lipid peroxidation in murine skin in vivo. UVB induced a dose-dependent increase in lipid peroxidation of skin extracts in vitro; however, lipid peroxidation in the skin in vivo remained unaffected at irradiation doses of less than 1.0 J cm-2 and decreased significantly at doses over 1.5 J cm-2 (P < 0.01). Time-delayed inhibition of lipid peroxidation in the skin in vivo was observed after irradiation at 1.5 J cm-2. Administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced lipid peroxidation (P < 0.05), while it suppressed the ear-swelling response (ESR), a biological marker of inflammation. By contrast, administration of sodium nitroprusside, an NO enhancer, suppressed lipid peroxidation (P < 0. 01), while it enhanced the ESR. Expression of inducible nitric oxide synthase (iNOS) was observed from 12 to 48 h postirradiation at doses of 0.4-1.6 J cm-2. The UVB-induced iNOS expression was markedly inhibited by L-NAME, suggesting that iNOS is a major enzyme in the production of NO. These results suggest that NO acts as a mediator of the inflammatory response in UVB-irradiated skin, and that lipid peroxidation is inversely regulated with the NO-mediated inflammatory response in vivo.


Assuntos
Peroxidação de Lipídeos/efeitos da radiação , Óxido Nítrico/fisiologia , Raios Ultravioleta/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Inibidores Enzimáticos/farmacologia , Inflamação/fisiopatologia , Peroxidação de Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Pele/efeitos da radiação , Fatores de Tempo
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