RESUMEN

Bax inhibitor-1 (BI-1) is an evolutionarily-conserved endoplasmic reticulum protein. The expression of BI-1 in mammalian cells suppresses apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. BI-1 has been shown to be associated with calcium (Ca(2+)) levels, reactive oxygen species (ROS) production, cytosolic acidification, and autophagy as well as endoplasmic reticulum stress signaling pathways. According to both in vitro and clinical studies, BI-1 promotes the characteristics of cancers. In other diseases, BI-1 has also been shown to regulate insulin resistance, adipocyte differentiation, hepatic dysfunction and depression. However, the roles of BI-1 in these disease conditions are not fully consistent among studies. Until now, the molecular mechanisms of BI-1 have not directly explained with regard to how these conditions can be regulated. Therefore, this review investigates the physiological role of BI-1 through molecular mechanism studies and its application in various diseases.

Asunto(s)

Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Estrés del Retículo Endoplásmico/fisiología , Humanos , Lisosomas/metabolismo , Modelos Biológicos , Especies Reactivas de Oxígeno/metabolismo , Respuesta de Proteína Desplegada/fisiología

RESUMEN

BACKGROUND AND OBJECTIVE: Although heme oxygenase-1 (HO-1) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of HO-1 on the proinflammatory mediators activated by nicotine and lipopolysaccharide (LPS) stimulation in human periodontal ligament (PDL) cells. MATERIAL AND METHODS: The production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and HO-1 proteins was evaluated by Western blot analysis. RESULTS: Lipopolysaccharide and nicotine synergistically induced the production of NO and PGE(2) and increased the protein expression of iNOS, COX-2 and HO-1. Treatment with an HO-1 inhibitor and HO-1 small interfering RNAs blocked the LPS- and nicotine-stimulated NO and PGE(2) release as well as the expression of iNOS and COX-2. CONCLUSION: Our data suggest that the nicotine- and LPS-induced inflammatory effects on PDL cells may act through a novel mechanism involving the action of HO-1. Thus, HO-1 may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.

Asunto(s)

Ciclooxigenasa 2/efectos de los fármacos , Hemo-Oxigenasa 1/farmacología , Lipopolisacáridos/farmacología , Nicotina/farmacología , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Ligamento Periodontal/efectos de los fármacos , Androstadienos/farmacología , Antracenos/farmacología , Línea Celular , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/análisis , Dinoprostona/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/genética , Humanos , Mediadores de Inflamación/análisis , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Metaloporfirinas/farmacología , FN-kappa B/efectos de los fármacos , Óxido Nítrico/análisis , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Ligamento Periodontal/citología , Ligamento Periodontal/enzimología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Protoporfirinas/farmacología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Transfección , Wortmanina

RESUMEN

BACKGROUND AND OBJECTIVE: Although substance P (SP) stimulates bone resorption activity and this is reported to be correlated with the degree of periodontal inflammation, it is unclear how human periodontal ligament cells regulate neuropeptide-induced osteoclastogenesis or the possible involvement of heme oxygenase-1 (HO-1) might be. This study examines how SP affects osteoprotegerin (OPG) and RANKL expression via HO-1. MATERIAL AND METHODS: Using immortalized human periodontal ligament cells, the effects of SP on the expression of HO-1, RANKL and OPG mRNA and proteins were determined by RT-PCR and western blotting, respectively. Various concentrations of SP (10(-7), 10(-8), 10(-9) and 10(-10) m) were added to the medium, and the cells were treated for 0, 0.25, 0.5, 1, 2 and 3 d. RESULTS: Substance P upregulated RANKL and HO-1 and downregulated OPG mRNA and protein expression in periodontal ligament cells, in a concentration- and time-dependent manner. A HO-1 inducer inhibited both the upregulation of RANKL expression and downregulation of OPG expression by SP in periodontal ligament cells. By contrast, treatment with a HO-1 inhibitor or HO-1 small interferring RNA (siRNA) enhanced SP-stimulated RANKL expression. Inhibitors of ERK and p38 MAP kinases, phosphoinositide 3-kinase and nuclear factor-kappaB blocked the effects of SP on RANKL expression in periodontal ligament cells. CONCLUSION: These results suggest that SP stimulates osteoclastic differentiation by increasing the expression of RANKL vs. OPG via the HO-1 pathway in periodontal ligament cells. The HO-1 pathway may be an effective therapeutic target for inhibiting chronic periodontitis involving alveolar bone resorption.

Asunto(s)

Hemo-Oxigenasa 1/farmacología , Ligamento Periodontal/citología , Ligando RANK/efectos de los fármacos , Sustancia P/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Núcleo Celular/química , Citosol/química , Relación Dosis-Respuesta a Droga , Inducción Enzimática , Inhibidores Enzimáticos/farmacología , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/biosíntesis , Hemina/farmacología , Humanos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/análisis , FN-kappa B/antagonistas & inhibidores , Osteoclastos/efectos de los fármacos , Osteoprotegerina/efectos de los fármacos , Osteoprotegerina/metabolismo , Ligamento Periodontal/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Protoporfirinas/farmacología , Ligando RANK/metabolismo , ARN Interferente Pequeño/farmacología , Sustancia P/administración & dosificación , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores

RESUMEN

Pre-operative diagnosis of chest-wall deformity is important for successful surgical correction and post-operative evaluation of funnel chest patients. However, conventional indices that define the severity of deformity have several limitations; manually calculated and cannot supply information about asymmetry. We developed four indices that can represent both the depression and the asymmetry of the chest-wall, and can automatically be extracted by computerized image processing technique. Three indices, including eccentricity index (EI), flatness index (FI), and circularity index (CI), were suggested to represent the depression of the chest-wall, and one index, rotation index (RI), to represent the asymmetry of the chest-wall. To verify the feasibility of new indices, several synthetic images and real CT images were used to analyze the performance of new indices and the statistical relationship with conventional Haller index. The experimental results showed possible application of suggested indices to the diagnosis of funnel chest patient. Suggested indices showed clear trends of change with the severity of chest-wall deformation in regards to both the depression and the asymmetry. Results of statistical analysis showed high correlation between new indices and HI, showing possibility of replacing HI.

Asunto(s)

Tórax en Embudo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Adolescente , Adulto , Algoritmos , Preescolar , Estudios de Factibilidad , Tórax en Embudo/patología , Humanos , Tomografía Computarizada por Rayos X

RESUMEN

OBJECTIVES: Heme oxygenase (HO)-1 expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation has an ability to inhibit tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. Costunolide has been reported to inhibit IL-1 production, but whether other cytokines could be inhibited remains to be confirmed. We investigated the effects of costunolide and its components (alpha-methylene-gamma-butyrolactone; CH2-BL, alpha-methyl-gamma-butyrolactone; CH3-BL, and gamma-butyrolactone; BL) on HO-1 expression as well as TNF-alpha and IL-6 production in RAW264.7 macrophages. METHODS: HO-1 expression and Nrf2 nuclear accumulation were analyzed by Western blot analysis. The production of TNF-alpha and IL-6 in RAW264.7 macrophages stimulated with lipopolysaccharide (LPS) was assayed by ELISA. RESULTS: Costunolide and CH2-BL induced HO-1 expression and Nrf2 nuclear accumulation, whereas CH3-BL and BL did not. Pre-incubation with costunolide inhibited LPS-induced production of TNF-alpha and IL-6. The inhibitory effects of costunolide on TNF-alpha and IL-6 production were abrogated by tin protoporphyrin, an HO inhibitor. CONCLUSIONS: Costunolide is an effective HO-1 inducer capable of inhibiting macrophage-derived pro-inflammatory cytokines. CH2-BL moiety of costunolide is essential for Nrf2 activation leading to HO-1 expression.

Asunto(s)

Hemo-Oxigenasa 1/biosíntesis , Interleucina-6/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Sesquiterpenos/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , Transporte Activo de Núcleo Celular , Animales , Antiinflamatorios no Esteroideos/farmacología , Línea Celular , Núcleo Celular/metabolismo , Inducción Enzimática , Interleucina-6/biosíntesis , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/farmacología , Protoporfirinas/farmacología , Factor de Necrosis Tumoral alfa/biosíntesis

RESUMEN

In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.

Asunto(s)

Osteoporosis Posmenopáusica/prevención & control , Ovariectomía , Placenta/fisiología , Extractos de Tejidos/farmacología , Animales , Biomarcadores , Fenómenos Biomecánicos , Peso Corporal/efectos de los fármacos , Densidad Ósea , Huesos/patología , Recuento de Células , Progresión de la Enfermedad , Femenino , Cuello Femoral/patología , Humanos , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoporosis Posmenopáusica/patología , Placenta/química , Embarazo , Ratas , Ratas Sprague-Dawley , Extractos de Tejidos/química , Malla Trabecular/citología , Malla Trabecular/efectos de los fármacos

RESUMEN

Yuk-Hap-Tang (YHT) induces cell death in human cervical carcinoma HeLa cells. Caspase-3, -6 and -9 were markedly activated in HeLa cells treated with YHT. The preferred substrate for caspase-3 cysteine protease, PARP, was cleaved to its 85-kDa cleavage product. YHT increased the amount of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax. Although p53 has been reported to accumulate in cancer cells in response to anticancer agents, the p53 expression level was not changed in HeLa cells treated with YHT. Manganese (Mn)-TBAP, a mitochondria-specific SOD mimetic agent and NAC/GSH (N-acetyl cysteine/ reduced glutathione) reduced the YHT-induced cytotoxicity and decreased the number of the YHT-induced apoptotic cells. Furthermore, YHT reduced the expression of Mn-SOD protein and its activity in HeLa cells. The data demonstrate that YHT induces the apoptosis of human cervical carcinoma HeLa cells by intervening Mn-SOD.

Asunto(s)

Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Medicina Tradicional de Asia Oriental , Extractos Vegetales/farmacología , Superóxido Dismutasa/genética , Caspasas/metabolismo , Supervivencia Celular/efectos de los fármacos , Depuradores de Radicales Libres/metabolismo , Células HeLa , Humanos , Cinética , Corea (Geográfico) , Fitoterapia , Superóxido Dismutasa/efectos de los fármacos

RESUMEN

The effect of capsule circulation velocity and volumetric oxygen transfer coefficient on the production of L-lysine by encapsulated Corynebacterium glutamicum in an airlift bioreactor has been evaluated. A larger oxygen supply in the airlift bioreactor caused a more than 58% increase in L-lysine productivity compared to that in a shaking flask incubator. The quantity of L-lysine produced during 5 h of cultivation in the airlift bioreactor was suggested to increase with increasing circulation velocity of the capsule in the bioreactor rather than with an increase in volumetric oxygen transfer coefficient.

RESUMEN

H2S dissolved in water can be converted to elementary sulfur or sulfate by the photosynthetic bacterium Chlorobium thiosulfatophilum. The effects of the light/dark cycle on cell growth and the rate of sulfide removal were investigated to develop an appropriate fermentation strategy. Dark fermentation was also studied without addition of H2S and CO2 as electron and carbon sources. Average specific growth rates of bacterial cultures with a continuous supply of H2S and CO2 both in light and dark conditions were occurred in the range of 0.008 to 0.009 h(-1), indicating little dependence on the light/dark cycle, but about 25% of the growth rate that was occurred only in the presence of light. Average H2S removal capacities for cultures grown under the light/dark cycles of 14/10 , 12/12 , and 9/15 h, respectively, with a continuous supply of feed gases, were 0.08, 0.07, and 0.04 micromol H2S.min(-1)/mg protein.l(-1) in the dark, and was slightly less than those in the light. H2S removal capacity with variation of the light/dark cycle was about 30-60% of that obtained in the continuously illuminated cultures. ATP concentration in the dark decreased from 0.43 to 0.37 mg ATP.mg protein(-1) as the daily dark duration decreased from 15 to 10 h. The production rate for lactic acid from a culture grown without a supply of mixtures of H2S and CO2 gases was 0.218 g lactic acid.l(-1).h(-1), much more than that grown with a supply of feed gas mixtures. Time-averaged concentrations of lactic acid produced overall during the light and dark periods were 13.7 g lactic acid.l(-1) during the light/dark cycle of 14/10 h without a supply of feed gas, and 3.1 and 2.4 g lactic acid.l(-1) during the cycles of 9/15 and 14/10 h, respectively, with a supply of feed gas.