REGULATION OF KALLIKREIN MK9 IN HYPERTENSION

Meharry Medical College, Nashville TN

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from applicant's abstract): This seeks funding to retrain, to acquire additional technical skills, and to gain hand-on experience on the state-of-the-art molecular biology techniques. This retraining, and acquirement of additional state- of-the-art technical skills will help the candidate not only in gaining cutting-edge technology experience but also making him competitive in seeking R01 type funding. The experience gained by the candidate will be applied to the proposed investigation in the evaluation of altered gene regulation of epidermal growth factor- binding protein (EGF-BP C), (Kallikrein mK9),a prorenin converting enzyme in mice genetically selected for high blood pressure. The funding will also provide opportunity to train minority students in the area related to cardiovascular diseases. Preliminary results of the proposed investigation, utilizing the submandibular gland(whole issue) from mice genetically selected for high blood pressure, indicated increase expression of EGF-BP C(kallikrein mK9), a prorenin converting enzyme. Immuno- histochemical localization of this kallikrein indicated it to be present in the submandibular gland duct cells. It is hypothesized that higher expression of this prorenin converting enzyme is due to altered activity of its gene MKlk-9. The main objective of the proposed investigation is to evaluate the molecular mechanism of the up regulation of EGF-BP C in long-term duct cell cultures. Specific aims to test the hypothesis include development of long- term duct cell cultures, quantitation and steady state levels of EFG-BP specific mRNA, mutational changes in the promoter region of EGF-BP C gene (mKlk-9), and evaluation of transcription factor binding to the promoter region of this kallikrein. This research will be conducted in the mentor's laboratory, Department of Biochemistry, Vanderbilt University and the candidate's laboratory, Department of Anatomy and Physiology, Meharry Medical College. Both of these laboratories are located in Nashville, TN. During retraining, facility will be developed with techniques, data collected and affiliation developed will further the missions of Meharry Medical College.