Soluble guanylyl cyclase expression is reduced in allergic asthma

Papapetropoulos, Andreas, Camargo Madeira Simoes, Davina, Xanthou, Georgia, Roussos, Charis and Gratziou, Christina (2006) Soluble guanylyl cyclase expression is reduced in allergic asthma. AJP: Lung Cellular and Molecular Physiology, 290 (1). L179-L184. ISSN 1040-0605

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Soluble guanylyl cyclase (sGC) is an enzyme highly expressed in the lung that generates cGMP contributing to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in sGC expression, we used a well-established murine model of allergic asthma. Histological and biochemical analyses confirmed the presence of inflammation in the lungs of mice sensitized and challenged with ovalbumin (OVA). Moreover, mice sensitized and challenged with OVA exhibited airway hyperreactivity to methacholine inhalation. Steady-state mRNA levels for all sGC subunits (α1, α2, and β1) were reduced in the lungs of mice with allergic asthma by 60–80%, as estimated by real-time PCR. These changes in mRNA were paralleled by changes at the protein level: α1, α2, and β1 expression was reduced by 50–80% as determined by Western blotting. Reduced α1 and β1 expression in bronchial smooth muscle cells was demonstrated by immunohistochemistry. To study if sGC inhibition mimics the airway hyperreactivity seen in asthma, we treated naïve mice with a selective sGC inhibitor. Indeed, in mice receiving ODQ the methacholine dose response was shifted to the left. We conclude that sGC expression is reduced in experimental asthma contributing to the observed airway hyperreactivity.

Item Type: Article
Subjects: B100 Anatomy, Physiology and Pathology
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Sport, Exercise and Rehabilitation
Depositing User: Becky Skoyles
Date Deposited: 19 Dec 2017 12:37
Last Modified: 12 Oct 2019 11:47

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