Proteomics Study Reveals Profound Gender-related Differences in Lung Responses to Cigarette Smoke

Changes in cell signaling proteins are induced at lower doses in female
rats compared to males

VANCOUVER, Aug. 4, 2011 /PRNewswire/ – Kinexus Bioinformatics Corporation, a
world-leader in molecular intelligence research, announced today the
publication of the results from a major study undertaken in
collaboration with the A. W. Spears Research Center, Lorillard Tobacco
Company to uncover cigarette smoke protein biomarkers. The findings
appear in the Journal of Proteome Research (http://pubs.acs.org/doi/abs/10.1021/pr200345y) and reveal profound differences in the responses of many lung proteins
in male and female rats exposed to dilute mainstream smoke for 3 hours
per day for 5 consecutive days. The data is also available online with
open-access in the Kinexus KiNET DataBank (http://www.kinexus.ca/ourServices/kinet/kinet.html).

Using the Kinexus integrated platform of proteomics discovery services,
the researchers initially analyzed lung lysates that were pooled from
similar groups of exposed rats using antibody microarrays that tracked
over 500 key cell signaling proteins for their abundance and their
phosphorylation status. Phosphorylation acts as an on/off switch for
most of the 23,000 proteins encoded by the human genome. Promising
leads from these antibody microarrays were confirmed by immunoblotting
studies, and they were further monitored using microarrays that were
printed with lysates from individual animals as separate spots on the
chips. Over 20 signal transduction and stress proteins were found to be
consistently and significantly altered with the short term cigarette
exposures, and bioinformatics was used to show how these proteins
connected within cell signaling networks.

Smoke-altered proteins regulate apoptosis, proliferation, stress
response, cell structure, cell migration and inflammation. The female
rats demonstrated much higher sensitivity to low doses of cigarette
smoke and resultant changes in these protein pathways than their male
counterparts. The study utilized proteomic technologies to enable a
systematic approach to understanding lung proteins altered by smoke.

“This study demonstrates the robustness of antibody-driven proteomics to
discover useful biomarkers” commented one of the authors of the
scientific publication Dr. Steven Pelech, President and Chief
Scientific Officer of Kinexus and a professor in the Department of
Medicine at the University of British Columbia. “Monitoring the
expression and phosphorylation of proteins is immensely more
challenging than genomic analyses, but is more insightful for guiding
biomedical researchers in finding biomarkers for understanding the
pathology of disease induced by toxins in the environment.”

For 12 years, Kinexus has been a unique provider of proteomics services
to academic and industrial laboratories to track protein kinases and
their phosphoprotein targets in experimental tissue and cell specimens.
The company has developed a diverse panel of microarrays and
complementary technologies that can monitor the presence and activity
levels of hundreds of signaling proteins, their interactions, and the
effects of promising drug candidates. The application of this knowledge
positions Kinexus and its clients for improved disease diagnosis and
personalized drug therapies to improve human health.

SOURCE Kinexus Bioinformatics Corporation