The following investigations are under way in the Department of Physiology within the School of Medicine at Meharry.

Regulation of the expression of G[alpha]i2 by reactive oxygen species
: Ifeanyi J. Arinze, Ph.D.
Funding Source: National Cancer Institute (NCI)
Project Summary: Oxygen radicals, also known as reactive oxygen species (ROS), are products of normal cell metabolism but they are toxic at high levels. They can be induced by drugs, environmental oxidants, and stress-inducing chemicals. ROS and the signal transduction proteins called G proteins are of enormous significance in public health because abnormalities in their function impact many diseases such as diabetes, heart failure, hypertension, atherosclerosis, and cancer. The outcome of Dr. Arinze's research will contribute to further understanding of these pathologies.

Effect of antioxidant enzymes on BaP-induced atherogenesis 
: Zhongmao Guo, M.D., Ph.D.
Funding Source: National Institute of Environmental Health Sciences (NIEHS)
Project Summary: Benzo[a]pyrene (BaP) is an environmental pollutant. Besides inducing cancers in humans, BaP has been shown to promote the development of atherosclerosis, which is the primary cause of coronary heart disease and stroke. The mechanism underlying the atherogenic action of BaP remains unknown. A currently popular theory postulates atherosclerosis as an inflammatory process driven by reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. BaP has been shown to increase intracellular ROS. Thus, Dr. Guo's is looking to see if generation of ROS in vascular cells is a key mechanism by which BaP promotes atherogenesis.

 Defective isoforms of ApoE induce atherogenesis via unfolded protein responses
Researcher: Hong Yang, M.D
Funding Source: National Heart, Lung and Blood Institute (NHLBI)
Project Summary: Dr. Yang is studying the involvement of unfolded protein response in foam cell formation, an early stage of atherosclerosis. Data derived from this project will contribute to understanding of the mechanism of atherosclerosis and provide therapeutic strategies for myocardial infarction and stroke induced by atherosclerosis.

 Estrogen-neuroprotection due to astroglial glu transporters occurs via TGF-a/b1
Researcher:Eun-Sook Y. Lee, Ph.D.
Funding Source: National Institute of General Medical Sciences (NIGMS)
Project Summary: Impairment of astroglial glutamate transporters is associated with various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and manganism, which is caused by chronic manganese (Mn) exposure. Since tamoxifen (TX) and 17B-estradiol (E2) have been shown to be neuroprotective in various neurodegenerative diseases, Dr. Lee is testing whether E2/SERMs can exert neuroprotective effects by attenuating Mn-induced impairment of astroglial glutamate transporters. Moreover, Dr. Lee's team is testing whether growth factors, TGF-a/B, mediate E2/TX-induced restoration of glutamate transporters.

 Nitric oxide and gastric motility in female diabetics
: Pandu Gangula, Ph.D.
Funding Source: National Institute of Diabetes/Digestive/Kidney (NIDDK)
Project Summary: Diabetes causes several complications that affect retina, kidney, vascular, gastrointestinal, and nervous system. The mechanism through which diabetic complications develop is unclear. Gastric dysmotility or gastropathy is one of the vigorous complications of diabetic mellitus in clinics and can cause disabling symptoms including nausea, vomiting, and weight loss and often leads to delayed or accelerated gastric emptying. Although the exact pathogenesis remains unknown, there is fairly convincing evidence in experimental models that diabetes results in the malfunctioning of specific neurons that produce the neurotransmitter nitric oxide (NO). The data from Dr. Gangula's studies will provide important relevant, thereby enhance our understanding of the pathophysiology of gastroparesis.

 Human ApoE4 and Foam Cell Formation
Researcher:Zhongmao Guo, M.D., Ph.D.
Project Summary: The overall goal of this project is to determine the mechanism(s) leading to excess cholesterol accumulation in macrophages treated with apolipoprotein E4 (ApoE4)-enriched lipoproteins, and to elucidate the role of unfolded protein response (UPR) in this process. By elucidating the role that ApoE4-containing lipoproteins play in the formation of foam cells, an early event in the development of atherosclerosis, we will provide strategies for treatment or prevention of this disease.