NIEHS Grant Supports van der Vliet’s Research on Environmental Tobacco Smoke and Asthma
- By Jennifer Nachbur
In Albert van der Vliet’s laboratory, he and his research team work at what they refer to as “the interface of chemistry and biology” in order to gain a better understanding of how common airborne pollutants cause the type of lung cell injury, inflammation and remodeling that results in such lung diseases as asthma, chronic obstructive pulmonary disorder (COPD) and lung cancer.
A professor of pathology at the University of Vermont College of Medicine, van der Vliet is an expert in the area of oxidative stress and redox signaling and their importance in environmental lung diseases. His recent research has shown that reactive aldehydes, toxic chemicals found in the environment and in cigarette smoke, can react with cellular proteins and alter their function. These aldehydes, also known as electrophiles, are not only present in the environment but are also produced during inflammation or tissue injury as a result of oxidative stress, and can impact certain cell signaling pathways in lung cells by chemically modifying specific amino acid residues in critical proteins. According to van der Vliet, the aldehyde acrolein, a major electrophile in tobacco smoke, can mimic many of the known consequences of smoking or environmental tobacco smoke exposure, such as lung cell injury and changes in the immune responses that can cause increased susceptibility to infection and allergic lung disease.
A July 1, 2012 online article van der Vliet coauthored in the journal Nature Chemical Biology highlighted the potential importance of hydrogen sulfide (H2S) – a known airborne pollutant that was recently recognized as a gaseous mediator generated by human cells – in metabolizing and detoxifying acrolein and other electrophiles, and could therefore have the potential to be therapeutic. Specifically, van der Vliet and his UVM colleagues were able to demonstrate that the harmful properties of acrolein can be inhibited by silencing one of the enzymes involved in H2S biosynthesis.
With support from a five-year, $1.7 million grant from the National Institute of Environmental Health Sciences, van der Vliet and his team will now seek to determine the relevance of H2S in the context of environmental tobacco smoke and its effects – from a lung biology perspective – on asthma.
“A better understanding of the importance of acrolein in smoking-related diseases, and of the cellular pathways that control acrolein metabolism, may help clarify the associations between cigarette smoking and disease,” says van der Vliet.
The team’s work in this area, van der Vliet adds, could potentially lead to the ability to identify susceptible populations by examining genetic alterations within metabolic enzymes that detoxify electrophiles, such as acrolein.