Inactivation of pulmonary NAD+-dependent 15-hydroxyprostaglandin dehydrogenase by acrolein.
Acrolein, a highly reactive aldehyde found in cigarette smoke, was shown to induce time-dependent inactivation of NAD+-linked 15-hydroxyprostaglandin dehydrogenase from porcine lung. The inactivation process followed pseudo-first-order kinetics and was irreversible. Inactivation by acrolein can be prevented by prior incubation of the enzyme with GSH but not by subsequent addition of GSH during assay. Inactivation can be also protected fully by prior incubation of the enzyme with NAD+, but only partially with prostaglandin E1. The results suggest that acrolein alkylates the enzyme at the coenzyme binding site and inactivates the enzyme. Inactivation of pulmonary NAD+-linked 15-hydroxyprostaglandin dehydrogenase by acrolein may alter cellular and circulating thromboxane/prostacyclin ratios and subsequently disturb vascular homeostasis and augment inflammatory and anaphylactic responses in smokers.
D000171:Acrolein / Q000494:pharmacology*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D012907:Smoking; D013329:Structure-Activity Relationship; D013552:Swine; D013931:Thromboxanes / Q000378:metabolism
D000447:Aldehydes; D011453:Prostaglandins; D013931:Thromboxanes; D009243:NAD; D000171:Acrolein; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase