Dr. Bettye Sue Hennington, Biology Professor, has established the Proteomics/Mass Spectrometry Center. National epidemiological studies indicate that adults born at full term, low birth weight develop hypertension in significantly greater numbers than full term, normal birth weight adults. The labs of Dr. Hennington and collaborator Dr. Barbara Alexander, Associate Professor of Physiology and Biophysics at UMC, are interested in the development of hypertension in a unique intrauterine growth restriction (IUGR) or low birth weight rat model.
Preliminary studies show the adult male IUGR develops hypertension, while the adult female develops hypertension only if ovarectomized. While the rats are housed at UMC, rat kidney tissue and urine are sent to Tougaloo College. Using assays that detect reactive oxygen species (ROS), we have determined that adult IUGR hypertensive males exhibit increased oxidative stress and adult IUGR normotensive females have normal levels of ROS. Data from western blot analyses indicate a gender difference in the regulation of four antioxidant enzymes in the IUGR rats. Enzymes tested include catalase, Cu/Zn superoxide dismutase, Mn superoxide dismutase, and glutathione oxidase. Adult IUGR female urines indicate normal amounts of F2-isoprostanes, a breakdown product of the lipid arachindonic acid and the gold standard for determining oxidative stress in disease.
Future studies in oxidative stress will focus on the cellular activity of the four enzymes and real-time RT-PCR will be used to determine mRNA levels of each transcript. Fluorescent microscopy at the Tougaloo College facility will be used to verify the production of oxidative stress enzymes in the kidney and physiological changes in the rat kidneys will be followed from birth to adulthood in the rat model. Using the IUGR model, the lab will continue to follow mechanisms that are affected by oxidative stress including the role of nitric oxide production. The mRNA levels, protein levels, and activity levels of the three nitric oxide synthases, nNOS, iNOS, and eNOS will be determined in IUGR and normal rats, male and female. It is hypothesized that an increase in oxidative stress leads to a decrease in the activity and expression of the nitric oxide synthases and thus the production of nitric oxide leading to hypertension in the adult male IUGR. Mass spectrometry studies will determine the F2-isoprostane levels in the intact IUGR male, castrated IUGR male, and castrated and testosterone-supplemented IUGR male. Similar studies will be done using intact and ovarectomized females IUGR rats.
The lab’s undergraduates have been instrumental in determining optimal conditions for western blots and RT-PCR. Tougaloo undergraduates involved in the studies attend weekly seminars given by the researchers in the UMC Department of Physiology and Biophysics and attend Dr. Alexander’s lab meetings while interacting with members of the Alexander lab. They have learned to manage their projects, analyze their data, and determine the subsequent steps to be taken. The training in critical thinking skills and research presentations has been invaluable to the students’ career choices. Two of the ten students mentored in Dr. Hennington’s lab have begun their graduate education. Dr. Hennington has partnered with Dr. Erdogan Memili of Mississippi State University (MSU) to submit an NSF Undergraduate Research Mentoring proposal. This grant will provide two full-time undergraduate researchers for the TC PROTEOMICS lab and the opportunity for enhanced research training for the undergraduates at MSU during the summer months. Other internal and external stipends are also available for our undergraduate researchers.
Bettye Sue Hennington, Ph.D.
Associate Professor of Biology