Studies of Membrane Associated Energy Transduction Mechanisms in Pathological States: Chemical and Biochemical Studies of PGB sub x

摘要

PGBx, a derivative of 15-keto prostaglandin B1, protects oxidative phosphorylation in isolated mitochondria and tissues during ischemic insult. These unique activities suggest a potential therapeutic role for PGBx. The principal components of PGBx samples are oligomers containing 4 to 8 monomers of the 15-keto PGB1, but impurities formed during the hydroxide catalyzed oligomerization process are also present and difficult to remove. This program is responsible for the synthesis and purification of PGBx, testing samples, and studies of its in vitro and in vivo activity. Different procedures, including gel filtration, electro-focusing and chromatography have been evaluated to purify PGBx prepared in this laboratory and to determine if a separation of the different biological activities of the stock material can be achieved. C13-NMR studies indicate that PGBx is a simple oligomer with bonding between the chains. PGBx protects isolated rat hearts from damage during periods of hypoxia. These results demonstrate the unique pharmacological properties of PGBx and suggest its value in protecting tissues against hypoxia.