Overexpression of Human Senescence Marker Protein 30 in Mice Fails to Offer Protection Against Challenge with Organophosphorus Compounds
Abstract
To investigate the ability of human senescence marker protein 30 (SMP30) to offer protection against chemical warfare nerve agents in vivo, we produced a recombinant human SMP30 fusion protein with a hemaglutinin tag expressed using an adenovirus (AD-SMP30). A single intravenous injection of Ad-SMP30 into mice transduced the expression of SMP30 fusion protein in a dose and time dependant manner in the liver and diaphragm, but not in the plasma or other tissues examined in mice. Expression of SMP30 in liver and diaphragm was noted on day 2, reached peak levels on day 4 and declined thereafter. The expression levels of SMP30 achieved in the liver of Ad-SMP30 injected mice compared to the liver of mice injected with an Ad-null virus was ~10- to 25-fold higher on day 4. Despite these high levels of SMP30, mice challenged with supra lethal doses of diisopropylfluorophosphate, VX or soman did not gain any discernible protection. Time to death between the control animals and animals with elevated levels of human SMP30 was not significantly different. These results suggest that wild-type human SMP30 expressed in the tissues of mice failed to offer protection against lethal levels of organophosphorus compounds in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA555371
Entities
People
- Moonsuk Choi
- Nageswararao Chilukuri
- Neil S. Jensen
- Peethambaran Arun
- Veeraswamy Manne
- Vineela Aleti
Organizations
- United States Army Medical Research Institute of Chemical Defense