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La activación del canal TRPC por la tioredoxina extracelular.

Shang-Zhong Xu¹, Piruthivi Sukumar, Fanning Zeng

¹Institute of Membrane and Systems Biology, Garstang Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.

|January 4, 2008

Resumen

La tioredoxina extracelular activa los canales iónicos TRPC5 y TRPC1 rompiendo un puente disulfuro. Este mecanismo recién descubierto vincula la tioredoxina con la función celular, particularmente en la artritis reumatoide.

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Área de la Ciencia:

Biología de los canales iónicos.
Biología celular molecular Biología celular molecular.
Reumatología Reumatología.

Sus antecedentes:

Los canales del Potencial del Receptor Transiente de los Mamíferos (TRP, por sus siglas en inglés) funcionan como sensores celulares.
La identificación de los activadores endógenos y las funciones celulares de los canales TRP es un objetivo de investigación clave.
La tioredoxina extracelular, una proteína redox, tiene objetivos extracelulares en gran parte desconocidos.

Objetivo del estudio:

Investigar el mecanismo de activación de los canales TRPC5 y TRPC1.
Determinar el papel de la tioredoxina extracelular en la regulación de estos canales.
Para explorar las implicaciones para la artritis reumatoide.

Principales métodos:

Ensayos bioquímicos para estudiar la activación del canal por la tioredoxina.
Análisis de la expresión de TRPC5 y TRPC1 en sinoviocitos.
Estudios funcionales que implican el bloqueo de canales y la medición de la actividad secretora.

Principales resultados:

La tioredoxina reducida activa los canales homomultimeros TRPC5 y los heteromultimeros TRPC5-TRPC1.
La activación se produce a través de la interrupción de un puente disulfuro en el bucle extracelular de TRPC5.5.
TRPC5 y TRPC1 se expresan en los sinoviocitos de la artritis reumatoide y se activan por la tioredoxina.
El bloqueo de estos canales afecta la actividad secretora celular.

Conclusiones:

Se ha identificado un nuevo mecanismo de activación de los canales iónicos que involucra la tioredoxina extracelular.
Este mecanismo vincula la tioredoxina extracelular con la función celular, con una posible relevancia para la artritis reumatoide.
Los canales TRPC5-TRPC1 representan un nuevo objetivo terapéutico para las enfermedades inflamatorias articulares.