case western reserve university





Ronald J. Przybylski, Ph.D.

Skeletal Muscle Development

The cell biology and physiology involved in the cell-cell interactions of skeletal myoblasts to form multinucleated myotubes is being studied. This is a critical step in skeletal muscle development and regeneration after injury since the end product is the contractile cell. The molecular signals resulting in myoblast recognition and then fusion appear to be calcium regulated. Our previous studies showed that the intracellular calcium content and the cell surface concentration are both critical for myoblasts to progress to the cell recognition and cell fusion stages of development. Currently, we are studying the cell surface calcium sensors, calcium regulated cell surface phosphorylation and phosphatase activity and whether these events elicit transmembrane signals which regulate specific genes. Further, we are testing whether micro domains of the cell membrane exist which are involved in these calcium regulated cell surface events because myoblast fusion occurs in restricted regions of the cell membranes.

Selected References:

Przybylski, RJ., RG. MacBride and AC Kirby. Calcium regulation of skeletal myogenesis. I. Cell content critical to myotube formation. In Vitro Cell and Develop. Biol. 25: 830-838,1989.

Przybylski, RJ., SJ Davidheiser, V Szigeti and AC Kirby. Calcium regulation of skeletal myogenesis. II Extracellular and cell surface effects. Cell Calcium 15:132-142, 1994.

Przybylski RJ, V Szigeti and AC Kirby. Calcium regulation of skeletal myogenesis. IV A defined culture medium permissive for myotube formation and the use of the calcium antagonist lanthanum. In Vitro Cell Develop. Biol. 22:402-406, 1986.

Bright, GR, NT Kuo, D Chow, S Burden, C Dowe and RJ Przybylski. Delivery of macromolecules into adherent cells via electroporation for use in fluorescence spectroscopic imaging and metabolic studies. Cytometry 24:226-233, 1996.


Important Roles of Glucose and Oxygen in Newborns

Survival after birth is dependent on proper respiration and glucose metabolism. These phenomena are tightly interrelated to produce ATP. Our projects include: 1) insulin regulation of glucose uptake through the glucose transporter protein GLUT-4. 2) the basis for insulin resistance- insulin receptor vs. intracellular signaling vs. glucose transporter translocation; 3) the regulation of glucose uptake by hypoxia through the glucose transporter protein GLUT-1.

Selected References:

Johnston, V, V Franzini, S Davidheiser, RJ Przybylski, and RJ Kliegman. Insulin receptor number and binding affinity in newborn dogs. Pediatric Res. 29:611-614, 1991.

Przybylski, RJ, R Freeh, SR Vadlamudi and RM Kliegman. Skeletal and cardiac muscle cells from insulin resistant newborns become insulin sensitive in cell culture. Mol. Cell Biol. 3:817, 1992.

Kaiser N, Sasson S, EP Freener, N Boukobza-Vardi, S Higashi, DE Moller, S Davidheiscr, RJ Przybylski and G King. Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes 42:80-89, 1993.

Kuo NT, RM Kliegman, and RJ Przybylski. Insulin resistance in newborns: insulin receptors, IRS- 1, phosphotidylinositol 3'-kinase and glucose transporters. Pediatric Res 35:204, 1994.

Pichiule P, JC Chavez, RJ Przybylski, and JC LaManna. Increase of neuronal nitric oxide synthase during chronic hypoxia. In: Oxygen Transport to Tissue XX (Advances in Experimental Medicine and Biology v.), edited by AG Hedetz and D Bruly, New York: Plenum Press, 1998, in press.


Survival Mechanisms During and After Heart Attacks

Ischemia/reperfusion injury is an important pathological process which is manifested clinically as reperfusion induced arrhythmias, myocardial stunning and an increase in the rate of cell death. Transient, intermittent ischemia, so-called ischemia pre-conditioning, produced experimentally or experienced as clinical angina promotes myocardial viability and mechanical function during a subsequent more severe heart attack. These events suggest that genes involved in cell survival have enhanced expression. The overall hypothesis that we are testing is that preconditioning mediates a protection of the myocardium by dramatically reducing the amount of apoptosis (programmed cell death) that occurs during ischemia and reperfusion. Cells undergoing apoptosis exhibit significantly altered ion homeostasis, gene expression, and ultimately loss of plasma membrane integrity. Apoptosis is regulated by the relative amounts of apoptotic (death) and anti-apoptotic (life) genes. Our preliminary results show that preconditioning leads to the enhanced expression of at least one anti-apoptotic gene and a shift in the ratio of life and death genes to favor life processes. We are investigating the possible altered expression of other related genes during experimental preconditioning and myocardial infarcts as related to myocardial contractility and ion homeostasis. Further, we are investigating whether chemical mimics of pre-conditioning used therapeutically work via expression of apoptotic and anti-apoptotic genes.

Dept. of Anatomy | 10900 Euclid Ave. | Cleveland, Ohio 44106-4930 | Phone:216.368.2433|
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