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Roy B. (Mac) McCauley, Ph.D.
Department of Pharmacology |
RESEARCH INTERESTS:
Ischemia is the reduction of arterial blood flow to a tissue. In heart muscle, this leads to oxygen deprivation and failure of the mitochondria to produce cellular energy. Upon restoration of blood flow (that is, reperfusion), the myocytes become reoxygenated, and various free radicals of oxygen are formed. These free radicals cause to cellular damage which, in turn, can lead to cell death by either apoptosis or necrosis. Ischemia/reperfusion injury is the pathological mechanism that causes tissue death in heart attacks and in stroke.
Our current research, carried out in collaboration with Dr. Tiziano Scarabelli, has the main objective to test the ability of new pharmacological agents to protect cardiac cells from ischemia/reperfusion injury. In addition, we are interested in investigating the molecular mechanisms whereby these pharmacological agents exert cardioprotection.
Some of our most interesting work involves urocortin, a 40 amino acid peptide that is related to the corticotrophin releasing factor (CRF) family. Urocortin is endogenously synthesized by several organs, including the heart. Importantly, its synthesis and release are increased during cardiac ischemia, where urocortin acts to protect myocytes against injury upon binding to its cognate receptors on the surface of cardiac cells. We recently documented that cardiac urocortin is released in the blood stream of rats exposed to ischemia/reperfusion injury before the occurrence of myocyte necrosis and apoptosis. Therefore, the quantification of urocortin serum levels may be clinically useful in the diagnosis of heart attacks. We also documented that administration of exogenous urocortin before, during or after ischemia reduces myocyte cell loss in cellular and animal models of ischemia/reperfusion injury. In our most recent work, we have found that binding of urocortin to its cognate receptors activates an intracellular signaling cascade in cardiac myocytes. This cascade involves early phosphorylation of the proto-oncogene Src, which leads to activation of ERK1/2, and eventually mediates the cardioprotective effect against ischemia/reperfusion injury.
SELECTED RECENT PUBLICATIONS
Knight R, Chen-Scarabelli C, Yuan Z, McCauley RB, Di Rezze J, Scarabelli GM, Townsend P, Latchman D, Saravolatz L, Faggian G, Mazzucco M, Chowdrey H, Stephanou A, Scarabelli TM. Cardiac release of urocortin precedes the occurrence of irreversible myocardial damage in the rat heart exposed to ischemia/reperfusion injury. FEBS Letter. 2008 Mar 19;582(6):984-90.
Chen Scarabelli C, McCauley RB, Yuan Y, Di Rezze J, Patel D, Putt J, Raddino R, Allebban Z, Abboud J, Scarabelli GM, Chilukuri K, Gardin J, Saravolatz L, Faggian G, Mazzucco A, Scarabelli TM. Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion. Am J Cardiol. June 2008, in press.
Scarabelli TM, Townsend PA, Chen Scarabelli C, Yuan Z, McCauley RB, Di Rezze J, Patel D, Putt J, Allebban Z, Abboud J, Chilukuri K, Gardin J, Saravolatz L, Knight RA, Latchman DS, Stephanou A. Amino acid supplementation differentially modulates STAT1 and STAT3 activation in the myocardium exposed to ischemia/reperfusion injury. Am J Cardiol. June 2008, in press.
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