Q3137049 (Q3137049): Difference between revisions
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Project | Project Q3137049 in Spain | ||
Revision as of 22:12, 7 October 2021
Project Q3137049 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3137049 in Spain |
Statements
96,800.0 Euro
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121,000.0 Euro
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80.0 percent
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1 January 2018
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31 December 2021
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AGENCIA CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
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18087
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LOS INHIBIDORES DE PROTEASAS DEL TIPO BOWMAN-BIRK (IBB), PRESENTES EN SEMILLAS DE LEGUMINOSAS, INHIBEN POTENTE- Y ESPECIFICAMENTE PROTEASAS DEL TIPO TRIPSINA Y QUIMOTRIPSINA, SIENDO CONSIDERADAS COMO COMPUESTOS ANTINUTRICIONALES CUANDO SE INCLUYEN EN LA DIETA DE ANIMALES DE GRANJA. LOS IBB DIFICULTAN LA DIGESTION DE PROTEINAS Y DISPONIBILIDAD DE AMINOACIDOS CAUSADO POR LA INHIBICION DE LAS ENZIMAS DIGESTIVAS A TRAVES DE UN MECANISMO DE FEEDBACK NEGATIVO. LA REDUCCION/SUPRESION DE ESTOS EN LAS SEMILLAS DE GUISANTE PODRIA MEJORAR LA CALIDAD PROTEICA DE LOS PIENSOS. MEDIANTE COLABORACION INTERNACIONAL, HEMOS IDENTIFICADO RECIENTEMENTE UN DOBLE MUTANTE NULO DE GUISANTE PARA DOS GENES ESTRECHAMENTE LIGADOS, TI1 Y TI2, QUE CODIFICAN SUS PRINCIPALES INHIBIDORES DE PROTEASAS; DICHA MUTACION CAUSA UNA REDUCCION MUY SIGNIFICATIVA DE LA ACTIVIDAD INHIBIDORA DE TRIPSINA Y ABOLE LA ACTIVIDAD ANTI-QUIMOTRIPSINA. ESTUDIOS SOBRE LA UTILIZACION DE PROTEINAS DE GUISANTE EN AUSENCIA/PRESENCIA REDUCIDA DE LOS IBB EN LOS PIENSOS Y SUS EFECTOS EN PRODUCCION ANIMAL SON DE GRAN INTERES DESDE EL PUNTO DE VISTA CIENTIFICO Y PRODUCTIVO. _x000D_ DESDE EL PUNTO DE VISTA DE LA SALUD HUMANA, LOS IBB PARECEN JUGAR UN PAPEL MUY DIFERENTE, REVELANDOSE SUS EFECTOS PREVENTIVOS Y/O SUPRESIVOS DE PROCESOS CANCERIGENOS E INFLAMATORIOS DENTRO DEL TRACTO GASTROINTESTINAL (TGI). EL FUNCIONAMIENTO ABERRANTE DE CIERTAS SERIN PROTEASAS EN PROCESOS INFLAMATORIOS Y CANCERIGENOS DEL TGI HA LLEVADO A LA COMUNIDAD CIENTIFICA A INVESTIGAR EL POTENCIAL DE ESTOS IBB COMO MODULADORES DE SUS ACTIVIDADES PROTEOLITICAS. CANTIDADES FISIOLOGICAMENTE RELEVANTES DE IBB ACTIVOS ALCANZAN EL INTESTINO GRUESO DEBIDO A SU EXTRAORDINARIA RESISTENCIA A LAS CONDICIONES EXTREMAS DEL TRACTO GASTROINTESTINAL (PH ACIDO, ACCION DE ENZIMAS DIGESTIVAS Y ACTIVIDAD METABOLICA/PROTEOLITICA DE LA MICROBIOTA INTESTINAL). NUESTRO GRUPO HA INVESTIGADO RECIENTEMENTE EL EFECTO PREVENTIVO DE UN EXTRACTO DE ALBUMINAS DE GUISANTE ENRIQUECIDO EN IBB EN RATONES CON COLITIS ULCEROSA INDUCIDA MEDIANTE TRATAMIENTO CON DEXTRANO SULFATO SODICO (DSS); EL CONCENTRADO DE IBB REDUJO SIGNIFICATIVAMENTE EL DAÑO MACROSCOPICO, HISTOLOGICO Y MICROBIOGICO INDUCIDO POR DSS EN RATONES. ASIMISMO, HEMOS DEMOSTRADO UN EFECTO SIGNIFICATIVO DOSIS- Y TIEMPO-DEPENDIENTE EN LA PROLIFERACION DE CELULAS CANCERIGENAS COLORRECTALES TRAS TRATAMIENTO CON IBB DE GUISANTE, LENTEJA Y SOJA. NUEVAS EVIDENCIAS SUGIEREN QUE IBB EJERCE SUS PROPIEDADES ANTIPROLIFERATIVAS MEDIANTE INHIBICION DE CIERTAS PROTEASAS, PUDIENDO EL PROTEOSOMA SER UNA DE SUS DIANAS TERAPEUTICAS. ESTA PROPUESTA INVESTIGADORA CONTIENE TRES ELEMENTOS PRINCIPALES DE TRABAJO: 1) INVESTIGAR EL EFECTO DE LOS IBB EN LA UTILIZACION DE LAS PROTEINAS DE GUISANTE MEDIANTE DOS APROXIMACIONES DIFERENTES, IN VITRO A TRAVES DE UNA METODOLOGIA VALIDADA INTER-LABORATORIO QUE SIMULA LAS CONDICIONES DIGESTIVAS HUMANAS (INFOGEST), E IN VIVO INVESTIGANDO SUS EFECTOS EN EL RENDIMIENTO DE PRODUCCION ANIMAL (BROILERS); 2) INVESTIGAR LOS EFECTOS PREVENTIVOS DE UNA FRACCION DE ALBUMINAS DE GUISANTE ENRIQUECIDA O EN AUSENCIA DE INHIBIDORES DE PROTEASAS UTILIZANDO COMO MODELO PRECLINICO RATONES CON COLITIS INDUCIDA MEDIANTE DSS; Y 3) IDENTIFICAR ISOINHIBIDORES INDIVIDUALES IBB, CON VARIACION NATURAL O INDUCIDA, QUE MUESTREN CAPACIDAD DE INHIBIR POTENTE- Y ESPECIFICAMENTE LAS ACTIVIDADES PROTEOLITICAS DEL PROTEASOMA. (Spanish)
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PROTEINS OF THE BOWMAN-BIRK TYPE, A MAJOR PROTEASE INHIBITOR FAMILY IN LEGUME SEEDS, WHICH INHIBIT POTENTLY AND SPECIFICALLY TRYPSIN- AND CHYMOTRYPSIN-LIKE PROTEASES, HAVE RECEIVED MUCH ATTENTION OF THE SCIENTIFIC COMMUNITY AS ANTINUTRITIONAL PROTEINS WHEN INCLUDED IN FARM ANIMAL DIETS. THUS, BOWMAN-BIRK INHIBITORS (BBI) ARE INVOLVED IN NEGATIVE EFFECTS ON PROTEIN DIGESTION AND AMINO ACID AVAILABILITY CAUSED BY THE INHIBITION OF DIGESTIVE ENZYMES VIA A NEGATIVE FEEDBACK MECHANISM; REDUCTION OR REMOVAL OF THESE PROTEINS COULD GREATLY ENHANCE SEED PROTEIN QUALITY. IN AN INTERNATIONAL COLLABORATION, WE HAVE RECENTLY IDENTIFIED A PEA VARIANT AS A DOUBLE NULL MUTANT FOR THE TWO CLOSELY GENES ENCODING THE TI1 AND TI2 SEED PROTEASE INHIBITORS; AS A CONSEQUENCE, AN EXTREME REDUCTION IN TRYPSIN INHIBITORY ACTIVITY AND NULL CHYMOTRYPSIN INHIBITORY ACTIVITY WAS FOUND IN SEEDS. STUDIES TO INVESTIGATE THE EFFECTS OF PROTEASE INHIBITORS IN PEA PROTEIN UTILIZATION AND THEIR CONSEQUENCES IN ANIMAL PERFORMACE WOULD PROVIDE NOVEL KNOWLEDGE FOR SEED QUALITY IMPROVEMENT. _x000D_ FROM THE HUMAN HEALTH POINT OF VIEW, STRIKING ADVENCES HAVE BEEN MADE IN UNRAVELLING THE PREVENTIVE AND/OR SUPPRESSIVE EFFECTS OF BBI PROTEINS ON CARCINOGENIC AND INFLAMMATORY DISORDERS WITHIN THE GASTROINTESTINAL TRACT (GIT). ABERRANT FUNCTIONING OF SERINE PROTEASES IN INFLAMMATORY AND CARCINOGENIC PROCESSES WITHIN THE GIT HAS PROMPTED SCIENTISTS TO INVESTIGATE THE POTENTIAL OF PROTEASE INHIBITORS AS MODULATORS OF THEIR PROTEOLYTIC ACTIVITIES. PHYSIOLOGICALLY RELEVANT AMOUNTS OF BBI CAN REACH THE LARGE INTESTINE IN ACTIVE FORM DUE TO THEIR EXTRAORDINARY RESISTANCE TO EXTREME CONDITIONS (ACIDIC PH, ACTION OF DIGESTIVE ENZYMES AND PROTEOLYTIC/METABOLIC ACTIVITY OF INTESTINAL MICROBIOTA) WITHIN THE GIT. RECENTLY, WE HAVE INVESTIGATED THE PREVENTIVE EFFECT OF A PEA ALBUMIN EXTRACT ENRICHED IN BBI IN THE DEXTRAN SODIUM SULFATE (DSS) INDUCED COLITIS IN MICE; THE BBI CONCENTRATE AMELIORATED SIGNIFICANTLY DSS-INDUCED DAMAGE IN MICE. IN ADDITION, WE HAVE DEMONSTRATED A SIGNIFICANT CONCENTRATION- AND TIME-DEPENDENT DECREASE IN THE PROLIFERATION OF HUMAN COLORECTAL ADENOCARCINOMA CELLS, FOLLOWING TREATMENT WITH BBI VARIANTS FROM PEA, LENTIL AND SOYBEAN. THE EMERGING EVIDENCE SUGGESTS THAT BBI EXERT THEIR ANTI-PROLIFERATIVE PROPERTIES VIA PROTEASE INHIBITION; THE PROTEASOME HAS BEEN IDENTIFIED AS A POTENTIAL TARGET FOR BBI IN EARLY STAGES OF COLORECTAL CARCINOGENESIS._x000D_ THE PROPOSAL CONTAINS THREE MAIN WORK ELEMENTS: 1) TO INVESTIGATE THE EFFECT OF BOWMAN-BIRK INHIBITORS IN PEA PROTEIN UTILIZATION BY USING TWO DIFFERENT APPROACHES, AN HARMONIZED IN VITRO DIGESTION METHOD (INFOGEST) MIMICKING THE DIGESTIVE HUMAN CONDITIONS AND IN VIVO STUDY TO INVESTIGATE THEIR EFFECTS ON ANIMAL (CHICKEN) PERFORMACE; 2) TO INVESTIGATE THE PREVENTIVE EFFECTS OF A PEA ALBUMIN FRACTION IN THE PRESENCE OR ABSENCE OF PROTEASE INHIBITORS BY USING THE DSS INDUCED COLITIS MODE IN MICE; AND 3) TO IDENTIFY INDIVIDUAL BBI ISOINHIBITORS, BOTH NATURALLY-OCCURRING AND ENGINEERED BBI, WITH THE ABILITY TO INHIBIT POTENTLY THE PROTEASOME. (English)
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Granada
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Identifiers
AGL2017-83772-R
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