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Los S-nitrosotiolos señalan la respuesta ventilatoria a la hipoxia

A J Lipton¹, M A Johnson, T Macdonald

¹Kosair Children's Hospital Research Institute, Departments of Pediatrics, Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40202, USA.

|September 15, 2001

Resumen

La hipoxia desencadena un aumento de la ventilación a través de S-nitrosotiolos (SNOs) derivados de la hemoglobina desoxigenada. Esta vía, que involucra a S-nitrosoglutatión y gamma-glutamilo transpeptidasa, es crucial para regular la respiración.

Área de la Ciencia:

La bioquímica es la bioquímica.
Fisiología Fisiología Fisiología.
Regulación de las vías respiratorias.

Sus antecedentes:

Los mecanismos bioquímicos que vinculan la hipoxia con el aumento de la ventilación no se comprenden completamente.
El control ventilatorio es un proceso fisiológico complejo que implica múltiples vías de señalización.

Objetivo del estudio:

Para dilucidar la vía bioquímica responsable de la hiperventilación inducida por la hipoxia.
Para identificar moléculas específicas involucradas en señalar cambios respiratorios durante la desoxigenación.

Principales métodos:

Investigó los efectos de varios S-nitrosotiolos (SNOs) en la ventilación en el tracto nuclear solitario (NTS).
Se analizó el plasma de la sangre desoxigenada y oxigenada para la actividad ventilatoria.
Utilizó transpeptidasa gamma-glutamilo (gamma-GT) knockout en ratones para evaluar su papel.

Principales resultados:

La S-nitrosocisteinil glicina (CGSNO) y la S-nitroso-l-cisteína (l-CSNO) imitaban los efectos ventilatorios de la hipoxia.
El plasma de la sangre desoxigenada indujo cambios de ventilación, mediados por S-nitrosoglutatión (GSNO).
La actividad de gamma-GT fue esencial para la ventilación mediada por GSNO, como lo demuestra la respuesta hipóxica deteriorada en ratones con knockout gamma-GT.

Conclusiones:

Los S-nitrosotiolos derivados de la desoxihemoglobina son moléculas de señalización clave en la ventilación inducida por hipoxia.
La activación dependiente de gamma-GT del S-nitrosoglutatión es crítica para esta respuesta respiratoria.
La bioquímica del S-nitrosotiol juega un papel central en la regulación de la respiración.

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