Abstract

Secretory Phospholipase A2 (sPLA2) represents a diverse class of roughly 20 enzymes, 12 of which have been identified in humans. These isoforms can be distinguished based on their tissue distribution, structure, and regulation. These differences in structure between the isoforms lead to the question does the enzyme's ability to respond to physical changes in the membrane during apoptosis governed by structure. S49 cell apoptosis was initiated by treatment with either the glucocorticoid dexamethasone (6–48 h) or with the calcium ionophore, ionomycin. The rates of hydrolysis were compared with each treatment condition for various concentrations of snake venom and human groups (hG) IIA, V, and X isoforms. The data were analyzed using a model that explicitly evaluates both the adsorption of enzyme to the membrane surface (step 1) and subsequent binding of substrate to the active site (step 2). Increased hydrolysis during apoptosis appeared to reflect step 2 for both the snake venom and the hGX enzymes. In contrast, apoptosis promoted step 1 for hGV. For hGIIA, the kinetics were more complex suggesting additional mechanisms beyond these two steps. These observations are rationalized in terms of the structure of the various isozymes and physical changes during apoptosis, including reduction in the strength of lipid/neighbor interactions and increased bilayer surface charge.

Degree

College and Department

Life Sciences; Physiology and Developmental Biology

Rights

http://lib.byu.edu/about/copyright/