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Scientists Identify Natural Molecule Protecting Against Asthma

Posted on: Friday, 27 May 2005, 09:00 CDT

Scientists identify natural molecule protecting against asthma

LOS ANGELES, May 26 (Xinhua) -- US scientists reported on Thursday they have found a natural substance capable of protecting against asthma, a disease affecting millions of people.

The findings, also suggesting that impaired airway relaxation may be a more important cause of asthma than previously recognized, may yield a novel approach to therapy, said the researchers in the May 26 online version of the journal Science.

"In thinking about asthma, scientists have generally focused on processes that actively constrict airways or lead to inflammation, making it difficult to get air in or out," said Jonathan Stamler, principal investigator at Duke University Medical Center.

"We haven't paid much attention to how airways are normally kept open. Our findings suggest the disease may stem from a deficit in the natural bronchodilator that normally relaxes airways."

The researchers reported that this natural compound, nitrosoglutathione (GSNO), can help keep airways open. Mice with elevated levels of GSNO were much less susceptible than normal animals to getting asthma, and animals deficient for GSNO developed asthma.

People with asthma are also deficient in GSNO, said first author Loretta Que. Therefore, drugs that increase GSNO levels could offer a new approach to treating the airway obstruction in asthma.

"The mice closely resemble the human condition, which makes this particularly exciting as a potential new approach toward asthma therapy," Que said.

GSNO is a molecule in the nitric oxide family. Earlier studies have suggested that nitric oxide (NO) might regulate the dilation of airways, with the exhaled breath of patients with asthma showing elevated levels of NO. However, studies in which researchers have manipulated NO levels in mice did not change the animals' response to allergens.

More recently, evidence from the group indicated that a family of NO-carrying molecules called S-nitrosothiols (SNOs) might mediate NO's role throughout the body, and offer new therapeutic approaches to diseases of the heart, lung and blood.

Last year the researchers showed that SNOs played a critical role in septic shock, a common cause of death in intensive care units.

Earlier this year they showed that SNOs are deficient in the blood of patients with sickle cell disease. Now, the link between GSNO deficiency and asthma further suggests that SNOs might play a protective role in many diseases.

In the current study, the team examined the airway responses of normal mice and those lacking an enzyme called GSNO reductase, which breaks down SNOs. The Duke researchers earlier showed that the enzyme governs GSNO levels in many tissues, including the lung.

Normal mice prone to asthma exhibit increased GSNO reductase levels, resulting in lower concentrations of lung GSNO following allergen exposure, the researchers found. In contrast, mice with elevated GSNO were protected from the airway hyper-reactivity that makes breathing difficult in asthma.

"Our findings indicate that GSNO reductase is critical for regulation of airway tone under normal conditions and in response to allergic challenge, and that an imbalance of GSNO, and perhaps of other S-nitrosothiols, may contribute fundamentally to asthma," their paper said.

"Our results further suggest that the GSNO deficit seen in patients with asthma may result from increased GSNO reductase activity," Stamler noted, "the enzyme may therefore offer a novel target for therapies designed to alleviate airway obstruction."

Source: Xinhua News Agency - CEIS

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