Bastarrachea RA, Curran JE, Eugenia BV, Kent JJ, López-Alvarenga JC, Téllez-Mendoza J, Blangero J, Comuzzie AG

Idioma: Español
Referencias bibliográficas: 53
Paginas: 89-101
Archivo PDF: 188.39 Kb.

RESUMEN

El componente inflamatorio de la obesidad y la diabetes (DMT2) se ha establecido firmemente debido al descubrimiento de los vínculos causales entre mediadores inflamatorios como el factor de necrosis tumoral alfa (TNF-α) y la señalización del receptor de insulina, así como por la elucidación de mecanismos moleculares subyacentes mediados transcripcional y postranscripcionalmente por la cinasa c-Jun NH2-terminal (JNK) y el inhibidor de la cinasa del factor nuclear-kappa β modificado por IKK, cuyas funciones y expresión inhiben las acciones de la insulina. Ha sido demostrado recientemente que el retículo endoplásmico (ER) es el sitio clave donde las señales metabólicas son procesadas, integradas y transmitidas en forma de señales de sobrecarga o estrés, que dan lugar a la activación de JNK, IKK y, posiblemente, otros mecanismos inflamatorios. La eliminación de las proteínas ensambladas erróneamente (mal ensambladas) en el ER por retrotranslocación es una adaptación fisiológica muy importante para poder corregir la sobrecarga o congestionamiento (estrés) del retículo endoplásmico. Una nueva proteína llamada selenoproteína S de mamíferos ha sido recientemente identificada. Sus funciones putativas sobre la respuesta al estrés (sobrecarga) del retículo endoplásmico se encuentran íntimamente vinculadas a la respuesta inmune y a las vías de señalización inflamatorias. Dicha proteína es codificada por SEPS1 (también conocido como VIMP), que es un gen involucrado en la respuesta a la sobrecarga (estrés) del retículo endoplásmico, con participación también en el control inflamatorio. En este artículo presentaremos los vínculos entre la sobrecarga (estrés), la inflamación, las selenoproteínas y la enfermedad metabólica, particularmente la diabetes mellitus tipo 2 y discutiremos el impacto de la variación genética en la selenoproteína S y su influencia en la regulación de la respuesta inflamatoria.

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